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Columbia  ®inibergitp      , 

^cijool  oe  Bental  antJ  0tal  burger? 


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^tltxtntt  Eibrarp 


GOUT 


ITS     PATHOLOGY,    FORMS,     DIAGNOSIS 
AND     TREATMENT 


Originally  founded  on  the  Goulstonian  Lectures  on  ^'The 
Chemistry  and  Pathology  of  Gout"  delivered  by  the  author 
before  the  Royal  College  of  Physicians  of  London  in  1897 


BY 

ARTHUR   P.   LUFF 

M,D.,  B  Sc  ,  F  R.C.P.  (LoND.) 
PHYSICIAN   TO   ST.    MARy's   HOSPITAL 


THIRD    EDITION 


NEW     YORK 

WILLIAM    WOOD    AND    COMPANY 

MDCCCCVII 


PREFACE   TO    THE   THIRD    EDITION. 

In  the  present   edition   the  scope  of  the  book  has  been 

considerably    extended,    and    a    large    portion    of    it    has 

been    rewritten.      The    new    views    as    to    the    pathology 

and    causation    of     gout    are    fully    discussed,     and     due 

consideration    is    given    to    the    view    that    a    bacterial 

toxin    is    the    primary    cause    of    gout.      A    chapter    has 

been   added   on   the   differential   diagnosis   of   the   various 

chronic   diseases   of   the   joints,    which   it   is   trusted   will 

prove    of    use    in    the    distinction    of    gout    from    other 

joint    diseases.      The    various    forms    of    irregular    gout, 

and  the  clinical  features  of  gout  in  its  acute,  subacute, 

and  chronic  forms,  are  much  more  fully  dealt  with  than 

in    the    previous    editions.      Considerable    additions    have 

also  been  made   to   the  section   of  the  book  devoted  to 

treatment,    and    the    subject    of    diet    is    dealt    with    at 

much    greater    length.      Important    additions    have    also 

been    made    to    the    chapter   on    hydrotherapy   and   spa 

treatment. 

A.    P.    L. 


9,  Queen  Anne  Street,  London,  W. 
May,  1907. 


PREFACE   TO    THE    FIRST    EDITION. 

Part  I.  of  this  book  is  mainly  a  reproduction  of  the 
Goulstonian  Lectures  on  "  The  Chemistry  and  Pathology 
of  Gout,"  delivered  in  1897  before  the  Royal  College  of 
Physicians  of  London.  Part  II.  deals  with  the  causa- 
tion of  gout,  its  various  forms  and  its  diagnosis  and 
prognosis.  Part  III.  includes  a  series  of  investigations 
undertaken  with  the  object  of  ascertaining  the  various 
conditions  affecting  the  formation  and  removal  of  gouty 
deposits,  the  influence  of  alcoholic  drinks  on  the  gouty 
process,  the  solvent  effect  of  the  mineral  constituents 
of  various  vegetables  on  gouty  deposits,  and  the  value 
of  certain  drugs  in  effecting  the  removal  of  such 
deposits.  Part  IV.  deals  with  the  treatment  of  gout 
and  of  gouty  conditions,  especially  in  the  light  of  the 
knowledge  gained  by  recent  investigations.  The  sub- 
ject of  diet  has  been  carefully  dealt  with,  and  a 
classification  of  the  various  mineral  waters  is  given 
according  to  their  therapeutic  value  in  the  treatment 
of    the    various    forms    of    gout. 


Digitized  by  tine  Internet  Arciiive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/goutitspathologOOIuff 


CONTENTS. 

PART  L 
THE    PATHOLOGY    OF    GOUT. 

CHAPTER    I. 

URIC   ACID   AND   THE   PURIN   BODIES. 

PAGE 

Uric  acid  and  its  compounds — Theories  as  to  the  causation  of  gout 
— View  that  uric  acid  is  formed  from  nuclein — The  purin  bodies 
— Conclusions  concerning  the  estimation  of  urinary  purins         .        i 

CHAPTER    II. 

THE  FOIiMATION   OF   URIC   ACID. 

View  that  uric  acid  is  formed  in  the  kidneys — Views  as  to  the  asso- 
ciation of  gout  and  kidney  disease — View  that  the  liver  and 
spleen  produce  uric  acid — View  that  uric  acid  is  produced  in 
various  tissues — View  that  excess  of  uric  acid  is  the  result  of 
an  animal  diet       .........     24 

CHAPTER    III. 

PRIMARY   CAUSATION   OF  GOUT. 

The  uric  acid  compound  regarded  as  acting  passively  and  physically 
— The  uric  acid  compound  regarded  as  acting  as  a  poison  or 
irritant — Uric  acid  not  a  poison — Necrotic  changes  as  the 
primary  cause — Inflammatory  or  degenerative  changes  as  the 
primary  cause — -Nervous  disturbance  as  the  primary  cause — 
Excess  of  carbonaceous  material  as  the  primary  cause — A 
bacterial  toxin  as  the  primary  cause — The  liver  as  a  toxin 
destroyer       ..........     41 

CHAPTER    IV. 

AI,KAI<INITY   OF   THE  BI,OOD   IN  GOUT. 

Uric  acid  a  normal  constituent  of  the  blood — Diseases  associated 
with  an  excess  of  uric  acid  in  the  Blood — The  alkalinity  of  the 
blood  in  gout — The  alkalinity  of  the  blood  and  the  precipitation 
of  sodium  biurate  ........     66 


X  CONTENTS. 

CHAPTBR    V. 
THE  GOUTY  DEPOSIT. 

PAGE 

Formation  of  th.e  gouty  deposit — Conditions  influencing  tlie  deposition 
of  sodium  biurate — Determining  cause  of  the  gouty  deposit — 
The  lymph  circulation — Seats  of  uratic  deposits  in  gout — 
Anatomical  seat  of  the  deposit  in  cartilages      .  .  .  '85 


PART  IL 

AETIOLOGY    AND    VARIETIES    OF    GOUT— DIAGNOSIS 
AND    PROGNOSIS. 

CHAPTER    VI. 

^TIOI,OGY   AND    CI,INICA];  FEATURES. 

J^tiology     of     gout — Heredity — Immediate      exciting     cause — The  _ 
clinical  features  of  acute  gout — The  clinical  features  of  chronic 
gout — The  kidneys  in  chronic  gout  .  .  .  .  .  .101 

CHAPTER    VII. 

THE  UPONE  AND   UiaC  ACID. 

The  urine  in  gout — Uric  acid  excretion — Uric  acid  and  lorea  elimin- 
ation— The  amorphous  urate  deposit — Estimation  of  uric  acid 
— Gowland-Hopkins  method — Otto  Folin  method — Methods 
of  Dimmock  and  Branson — Plumbism  and  gout         .  .  ,112 

CHAPTER    VIII. 

IRREGUI,AR   GOUT. 

Irregular  gout  affectmg  the  alimentary  tract — Irregular  gout  affect- 
ing the  air-passages  and  lungs — Irregular  gout  affecting  the 
heart  and  vessels — Irregular  gout  affecting  the  nervous  system 
— Irregular  gout  affecting  the  geni  to -urinary  system — Irregular 
gout  affecting  the  skin — Irregular  gout  affecting  the  eye  and 
ear — Other  irregular  gout  affections — Retrocedent  or  metastatic 
gout 130 

CHAPTER    IX. 

DIFPERENTIAI,  DIAGNOSIS. 

The  differential  diagnosis  of  chronic  diseases  of  the  joints — Forms 
of  rheumatoid  arthritis — Distinction  of  gout  from  rheumatoid 
arthritis — Distinction  of  gout  from  rheumatism — Distinction 
of  gout  from  various  diseases  of  the  joints — Prognosis  in  gout     147 


CONTENTS.  xi 

PART  III, 

INVESTIGATIONS    OF   CERTAIN   POINTS    CONNECTED 
WITH    THE    TREATMENT    OF    GOUT. 

CHAPTER    X. 

SOI,UBHITY   OF   SODIUM   BIURATE. 

PAGE 

Influence  exerted  by  the  mineral  constituents  of  meat,  milk,  and 
vegetables  respectively  on  the  solubility  of  sodium  biurate — 
Relative  effects  exerted  by  the  mineral  constituents  of  various 
vegetables  on  the  solubility  of  sodium  biurate — Influence  exerted 
by  the  mineral  constituents  of  various  vegetables  in  retarding 
the  conversion  of  sodium  quadriurate  into  sodiixm  biurate — 
The  vegetables  most  beneficial  to  gouty  subjects      .  .  .    T72 

CHAPTER    XI. 

SOI.UTION   OF   GOUTY  DEPOSIT. 

Reasons  for  believing  that  the  removal  of  gouty  deposits  by  alkalies 
is  erroneous — Experimental  investigation  of  the  value  of  the 
various  alkalies,  piperazine,  and  lysidine  as  solvents  of  gouty 
deposits — Experimental  investigation  of  the  value  of  salicylates 
as  solvents  of  gouty  deposits  .  .  .  .  .  .  .198 

PART  IV, 

THE  TREATMENT  OF  GOUT  AND  OF  GOUTY 
CONDITIONS. 

CHAPTER    XII. 

'acute  and  chronic  gout  :    treatment  and  diet. 

General  principles  of  treatment — Examination  of  the  urine — Treat- 
ment of  acute  gout — The  action  of  colchicum — Diet  in  acute 
gout — Treatment  of  subacute  and  chronic  gout  —  Preventive 
treatment  of  gout — Local  treatment  of  gouty  joints — Electric 
light  and  superheated-air  baths — Cataphoresis  .  .  .215 

CHAPTER    XIII. 

treatment  of  irregui,ar  gout. 

The  treatment  of  the  various  forms  of  irregular  gout  —  Gouty 
dyspepsia — Hyperchlorhydria  — The  gouty  heart  —  Neuritis — 
Insomnia — Gouty  eczema — Gouty  glycosuria  and  diabetes — 
Retrocedent  or  metastatic  gout       -  .  .  .  .  .232 


xii  CONTENTS. 

CHAPTER    XIV. 
DIEX  IN  GOUT. 

PAGE 

General  principles  of  dieting — Digestibility  of  food — Chittenden's 
views — Animal  food — Purin-free  diet — Vegetable  food — Starchy 
and  saccharine  foods — Fruits — Beverages — Simplicity  of  meals 
— The  Salisbury  diet — Plan  of  diet  for  gouty  subjects       .  .241 

CHAPTER    XV. 

AI.COHOL   IN   GOUT. 

Alcoholic  drinks — Acidity  and  gout-inducing  power  of  wines  and 
beers — Cause  of  the  inducement  of  gout  by  wines  and  beers — 
Wines  least  injurious  to  the  gouty — Cider — Perry     .  .  -259 

CHAPTER    XVI. 

SPA,    BAI^NEOI^OGICAI,,    AND    CI.IMATIC  TREATMENT. 

Spa  treatment — Ionic  theory  and  radio-activity — The  uses  of  mineral 
waters  in  the  treatment  of  gout — Classification  of  mineral 
waters — The  simple  waters — Simple  alkaline  waters — Alkaline 
sulphated  waters — Alkaline  muriated  waters — Common  salt  or 
muriated  waters — Sulphur  waters — Hot  and  cold  mineral  waters 
— Choice  of  a  spa — Balneology — Climatic  treatment         .  .   265 

Index 285 


GOUT  :  ITS  PATHOLOGY,  FORMS, 
DIAGNOSIS  AND  TREATMENT. 

PART  L 
THE  PATHOLOGY  OF  GOUT. 

CHAPTER  I. 
URIC  AQD  AND   THE   PURIN  BODIES. 

Uric  acid  and  its  compounds — Theories  as  to  the  causation  of 
gout  —  View  that  uric  acid  is  formed  from  nuclein  —  The 
purin  bodies  —  Conclusions  concerning  the  estimation  of 
urinary  purins. 

Gout  is  the  manifestation  of  a  number  of  morbid  tenden- 
cies, some  of  which  may  be  inherited  and  some  acquired. 
If  the  joints  are  affected,  articular  or  regular  gout  results ; 
if  other  organs  or  tissues  are  affected,  then  irregular  gout 
is  produced. 

It  is  a  disease  which  is  due  to  faulty  metabolism, 
probably  both  intestinal  and  hepatic,  as  the  result  of 
which  some  toxin  or  toxins  are  produced  and  lead  to  an 
auto-intoxication,  which  is  an  early  factor  in  the  develop- 
ment of  the  gouty  condition.  This  auto-intoxication 
coincides  with  or  is  followed  by,  in  the  majority  of  cases, 
a  deposition  of  sodium  biurate  in  certain  of  the  joints  or 
tissues,  which  constitutes  the  climax  of  the  gouty  attack. 
I  cannot  but  think  that  with  our  increasing  knowledge  and 
experience  of  the  disease  uric  acid  and  its  salts  will  in  all 
probability  have  to  be  relegated  to  a  position  of  subsidiary 
importance  in  the  pathogenesis  of  gout.  The  joint  mani- 
festations  are   dependent   upon   much   more   general   and 


2  GOUT :    PATHOLOGY.  [Part  i. 

much  larger  conditions  than  a  mere  excess  of  uric  acid  in 
the  blood.  The  deposition  of  sodium  biurate  is  merely  the 
sign  of  the  disease,  not  the  essence  of  it.  The  generally- 
accepted  belief  that  the  primary  development  in  gout  is 
the  heaping  up  and  deposit  of  uric  acid  in  the  tissues  must 
be  regarded  as  quite  inadequate.  The  accumulation  of 
uric  acid  in  the  tissues  is  simply  one  of  the  symptoms  of 
gout,  and  must  not  be  taken  as  its  cause. 

Walker  Hall  states  that  gout  cannot  be  regarded  as  a 
state  of  simple  malnutrition  ;  it  is  rather  a  condition  of 
insufficient  cellular  resistance  against  the  absorption  of 
intestinal  poisons  or  auto-toxins,  characterised  by  the 
production  of  imperfectly  formed  metabolites,  which  act 
upon  some  tissues  as  irritants  and  in  others  excite  degenera- 
tive changes  that  permit  uratic  irifiltration. 

Gout  is  associated  with  the  presence  of  an  excess  of 
uric  acid  in  the  blood,  and  the  questions  that  will  be  first 
dealt  with  mainly  resolve  themselves  into  the  mode  or 
modes  by  which  the  uric  acid  is  produced  and  introduced 
into  the  blood,  the  source  or  sources  of  its  production, 
the  relationship  that  it  bears  to  the  gouty  paroxysm  and 
to  the  other  manifestations  of  gout,  and  the  factors  or 
conditions  which  influence  its  formation  and  its  injurious 
action. 

Uric  acid  and  its  compounds. — Uric  acid  is  a  bi- 
basic  acid,  the  formula  of  which  is  H2(C5H2N403).  This 
acid  forms  the  following  three  classes  of  salts  : — (i)  The 
neutral  urates,  in  which  a  metal  takes  the  place  of  all  the 
displaceable  hydrogen,  such  as  NaoQHoNiOs,  the  neutral 
sodium  urate.  (2)  The  biurates,  in  which  a  metal  takes 
the  place  of  half  the  displaceable  hydrogen,  such  as 
NaHCjHaNiOs,  the  sodium  biurate.  The  biurates,  al- 
though acid  salts  in  constitution,  are  not  acid  to  test  paper. 
(3)  The  quadriurates,  in  which  a  metal  takes  the  place 
of  one-fourth  of  the  displaceable  hydrogen  of  two  mole- 
cules  of   uric    acid,   such   as    NaHC6H2N403,   H^C5H2N403, 


Chap.  I.]  COMPOUNDS    OF   URIC   ACID.  3 

the  sodium  quadriurate.  Of  these  three  classes  of  salts 
the  neutral  urates  cannot  exist  in  the  living  organism, 
and  therefore  take  no  part  in  the  pathology  of  gout.  It 
is  also  important  to  understand  that  uric  acid  does  not 
and  cannot  exist  in  the  blood  in  the  free  state  under  any 
conditions  whatsoever.  Tlxe  sodium  quadriurate  is  the 
soluble  uric  acid  compound  which  is  originally  contained 
in  the  blood  of  gouty  subjects,  and  this  substance,  as  just 
mentioned,  is  a  derivative  of  two  molecules  of  uric  acid 
in  which  sodium  is  substituted  for  one-fourth  of  the  dis- 
placeable  hydrogen,  or,  in  other  words,  it  is  a  molecular 
combination  of  sodium  biurate  with  uric  acid.  This 
sodium  quadriurate  is,  however,  an  unstable  body,  and 
after  a  certain  time  it  unites  with  some  of  the  sodium  car- 
bonate of  the  blood  to  form  sodium  biurate,  which,  if 
produced  in  larger  quantities  than  the  fluids  of  the  body 
can  retain  in  solution,  becomes  deposited  in  various  struc- 
tures in  the  crystalline  form. 

This  conversion  of  sodium  quadriurate  into  the  biurate 
by  the  sodium  carbonate  of  the  blood  is  shown  in  the  fol- 
lowing   equation  : 


2  /NaHCsH.N.Og.H.C^H.N.OaN  +  Na.COg 

I  Sodium  Quadriurate  J  Sodium 

Carbonate 


4  NaHCjH^N^Oa  +  CO,  +  H,0 

Sodium  Biurate 

The  sodium  quadriurate  is,  [therefore,  to  be  regarded  as 
a  comparatively  soluble  but  very  unstable  compound,  whilst 
the  sodium  biurate  is  comparatively  insoluble  but  very 
stable. 

Tunnicliffe  and  Rosenheim  *  have  published  a  series 
of  experiments  from  which  they  conclude  that  there  is 
no  evidence  of  the  existence  of  quadriurates  as  a  third  order 
of  uric  acid  salts.  They  consider  that  the  so-called  quadri- 
urates consist  of   mixtures  in  varying  proportions  of   uric 

*  Lancet,   1900. 


4  GOUT:    PATHOLOGY.  '  [part  i. 

acid  and  biurates,  and  that  their  property  of  showing  the 
formation  of  uric  acid  crystals  under  the  influence 
of  water  is  due  to  the  dissolving  out  of  the  more  soluble 
biurate  moiety  and  a  change  in  physical  state  of  the  re- 
maining uric  acid. 

It  would  appear,  however,  that  it  is  quite  an  immaterial 
point  whether  the  quadriurates  are  regarded  as  molecular 
combinations  of  uric  acid  and  biurates,  or  as  physical 
mixtures  of  these  substances. 

Murexide  Test  for  Uric  Acid. — If  two  or  three  drops 
of  strong  nitric  acid  are  added  to  a  fragment  of  uric  acid 
in  a  porcelain  dish,  and  heat  is  gently  applied  until  all  the 
nitric  acid  is  driven  off,  a  reddish-coloured  residue  (alloxan) 
will  be  left.  If,  when  the  dish  is  cold,  a  few  drops  of 
solution  of  ammonia  are  added  to  this,  a  beautiful  crimson- 
purple  colour  is  developed,  due  to  the  production  of  mur- 
exide by  the  action  of  the  ammonia  on  alloxan.  This  is 
an  extremely  delicate  test,  and  the  one-hundredth  part 
of  a  milligramme  of  uric  acid  may  be  detected  by  this 
reaction. 

Theories  as  to  the  causation  of  gfout. — Of  the  vari- 
ous theories  to  account  for  the  production  of  gout  the 
humoral  theories  have  been  to  the  front  for  many  cen- 
turies at  various  periods  in  the  history  of  the  disease. 
Galen  was  one  of  the  first  to  teach  that  tophi  arose  from 
the  desiccation  of  collected  and  pathologically  altered 
humours. 

Cullen,  who  was  the  great  opponent  of  the  ancient 
humoral  theory  of  gout  in  the  latter  half  of  the  last  century, 
admitted,  however,  that  in  some  instances  a  peculiar 
matter  appears  in  gouty  patients,  but  he  considered  that 
it  was  the  effect  and  not  the  cause  of  the  malady.  Uric 
acid  was  discovered  in  the  urine  by  Scheele  in  1775,  and 
in  1787  Wollaston  demonstrated  its  presence  in  gouty 
concretions.  These  discoveries  did  not,  however,  bring 
to  light  the  important  part  played  by  uric  acid  in  gout. 


Chap.  I]  URIC    ACID    iN  BLOOD.  5 

It  was  in  1847  that  Sir  Alfred  Garrod  first  found  uric  acid 
in  the  blood  of  gouty  subjects  in  the  form  of  a  sodium 
salt.  The  discovery  of  uric  acid  in  the  blood  of  gouty 
patients  eventually  led  to  the  much-discussed  question  as 
to  whether  it  was  the  cause  or  the  result  of  gout.  Those 
who  held  the  former  view  were  in  their  turn  divided  as 
to  whether  the  uric  acid  compound  only  exerted  its  bane- 
ful effects  when  it  had  crystallised  out  of  the  blood  and 
had  become  deposited  in  the  affected  tissues,  or  whether, 
while  still  circulating  in  the  blood,  it  exercised  a  true 
toxic  influence. 

Cause  of  the  presence  of  uric  acid  in  the  blood 
in  gout. — The  next  question  to  consider  is  whether  the 
excess  of  uric  acid  present  as  quadriurate  and  biurate  in 
the  blood  in  gout  is  the  result  of  deficient  excretion,  of 
over-production,  or  of  deficient  destruction.  All  observers 
are  agreed  that  an  abnormal  quantity  of  uric  acid  in  the 
form  of  one  or  other  of  its  salts  is  found  in  the  blood  in 
gout.  This  overcharging  of  the  blood  with  uric  acid  must 
be  due  to  one  or  more  of  the  following  causes  : — (i)  Normal 
production  and  deficient  excretion  of  uric  acid  ;  (2)  over- 
production and  normal  excretion  of  uric  acid  ;  and  (3) 
diminished  destruction  of  uric  acid  by  imperfect  oxidation, 
or  by  some  other  means. 

Admitting  then  an  excess  of  uric  acid  in  the  blood  in 
the  form  of  quadriurate  or  biurate,  and  that  its  deposition 
therefrom  as  the  sodium  biurate  in  cartilages  and  other 
tissues  is  connected  with  the  gouty  paroxysm,  the  two 
questions  that  naturally  arise  are  :  (i)  Where  is  the  uric 
acid  formed  ?  (2)  How  is  the  uric  acid  formed  ?  It  will 
be  well,  therefore,  first  to  consider  the  various  views  as 
to  the  seat  or  seats  of  formation  of  uric  acid. 

View  that  uric  acid  is  formed  from  nuclein.— 
Mares  showed  a  few  years  ago  that  the  greatest  increase 
in  uric  acid  excretion  occurs  in  a  few  hours  after  a  meal, 
whereas   general   nitrogenous    catabolism,    as  indicated  by 


6  GOUT :    PATHOLOGY.  [part  i. 

the  amount  of  urea  excreted,  increases  more  slowly,  and 

does  not  reach  a  maximum  until  some  hours  later.     This 

was  explained  by  Horbaczewski  to  be  due  to  a  digestive 

leucocytosis,    and   the    consequent   increased   liberation   of 

nuclein  within  the  body.     Horbaczewski  *  has  shown  that 

uric  acid,  as     well  as  xanthin  and  hypoxanthin,  can  be 

prepared    from    spleen    pulp.     The    close    relationship    of 

these  three  bodies  to  one  another  is  shown  by  a  comparison 

of  their  formulae  : 

C6H4N^03     Uric  acid. 
C5H4N4O,     Xanthin. 
C^H^N^^O       Hypoxanthin. 

By  digesting  fresh  spleen  pulp  with  hot  water  till  changes 
set  up  by  bacterial  agency  are  started,  he  found  that  the 
fluid,  when  freed  from  albuminous  bodies,  contained 
xanthin  and  hypoxanthin,  but  no  uric  acid.  By  treating 
this  fluid  with  arterial  blood  and  keeping  the  mixture 
at  40°  to  50°  C,  uric  acid  forms  in  it  after  several  hours. 
A  similar  result  is  produced  by  using  as  the  oxidising  agent 
either  a  dilute  solution  of  hydrogen  peroxide,  or  an  abun- 
dant supply  of  atmospheric  air.  Horbaczewski  found 
that  the  nitrogen  contained  in  the  uric  acid  so  formed  was 
about  equal  in  amount  to  the  nitrogen  contained  in  the 
xanthin  and  hypoxanthin  (xanthin  bases).  So  that  there 
exist  in  the  spleen  nitrogenous  substances  which  can  be 
transformed,  at  all  events  in  part,  into  xanthin  bases  or 
into  uric  acid.  The  xanthin  bases  when  once  formed  can- 
not be  further  oxidised  into  uric  acid.  Horbaczewski  brings 
forward  proof  that  the  substance  which  yields  xanthin 
bases  and  uric  acid  is  the  nuclein  of  the  spleen  cells.  It 
was  found  that  when  pure  nuclein,  prepared  from  spleen 
pulp,  was  dissolved  in  very  weak  alkali,  and  digested  with 
blood  at  40°  C,  uric  acid  was  formed.  Sadowenj  and  For- 
manck  have  shown   that  uric  acid  can  be  prepared  in  a 

*  Beiirdge  zur  Kentnisse  der  Bildung  der  Harnsdure  und  der  Xanthinhasen. 
Sitzungsbericht  der  K.  Acad.  d.  Wiss.  in_Wien.     C,  iii.,   1891. 


c„xr.  1.]  URIC    ACID   AND   NUCLEIN.  7 

similar  manner  from  almost  all  tlie  tissues  and  organs  of 
the  body,  and  conclude  that  the  nuclein  contained  in  the 
cells  is  the  mother-substance. 

It  having  thus  been  shown  that  uric  acid  could  be 
prepared  from  nuclein  outside  the  system,  an  attempt 
was  next  made  to  ascertain  whether  a  similar  decomposi- 
tion could  also  occur  in  living  human  beings.  Horbac- 
zewski  found  that  the  excretion  of  uric  acid  can  be  in- 
creased either  by  the  administration  of  nuclein  with  food, 
or  by  the  subcutaneous  injection  of  a  solution  of  it.  Umber* 
found  that  the  administration  of  a  large  amount  (500 
grammes  per  diem)  of  food  like  thymus,  which  contains  a 
considerable  quantity  of  nuclein,  increases  the  excretion 
of  uric  acid  as  compared  with  its  excretion  when  a  similar 
amount  of  flesh  is  given.  The  same  amount  of  liver  given 
to  one  person  caused  an  effect  similar  to  that  caused  by 
thymus,  but  in  others  its  action  was  less  marked.  Kidney 
and  brain  administered  as  food  yielded  nearly  the  same 
amount  of  uric  acid  as  flesh. 

From  his  experiments  Horbaczewski  concludes  that 
uric  acid  is  formed  in  health  by  the  disintegration  of  nuclein , 
and  that  sudden  variations  in  uric  acid  production  may 
be  due  to  the  breaking  up  of  leucocytes  and  conversion  of 
their  nuclein  into  uric  acid  or  xanthin  bases  within  the 
system.  It  has  been  shown  by  many  observers  that  a 
temporary  or  permanent  leucocytosis  is  always  accom- 
panied by  an  increased  excretion  of  uric  acid.  A  relation- 
ship between  the  number  of  leucocytes  in  the  blood  and 
the  excretion  of  uric  acid  is  observable  in  human  beings 
during  fasting  and  after  taking  food.  During  fasting  the 
number  of  leucocytes  diminishes,  and  the  amount  of  uric 
acid  excreted  falls  ;  after  taking  food  the  number  of  leu- 
cocytes increases,  and  the  amount  of  uric  acid  excreted 
rises.  The  increase  in  the  number  of  leucocytes  in  the 
blood  after  a  meal  appears  to  be  due,  at  all  events  in  part, 

*  Zeiischrift  /.    klin.   Medicin,   1896,   xxix.,   pp.    174-189. 


8  GOUT :    PATHOLOGY.  [Part  i. 

according  to  Hofmeister,*  to  the  rapid  increase  of  lymph 
cells  in  the  adenoid  tissue  of  the  stomach  and  intestines 
during  digestion,  whence  they  are  discharged  into  the 
lymph  stream,  and  finally  into  the  blood.  Gamprecht  f 
— who  uses  the  term  "  alloxur  bodies  "  in  Kossel  and 
Kriiger's  sense  as  meaning  those  bodies  which  have  an 
alloxan  and  urea  nucleus,  and  therefore  as  including,  be- 
sides uric  acid,  xanthin,  guanin,  hypoxanthin,  adenin, 
and  their  derivatives — found  that  in  the  exceptional  cases 
of  leukaemia  in  which  the  uric  acid  excretion  is  normal 
or  diminished,  the  alloxur  bases  are  increased,  and  that 
their  amount  varies  directly  with  the  amount  of  leucocytosis. 
He  gives  one  case  of  his  own  in  which  this  is  shown  very 
clearly,  and  points  out  that  it  forms  an  additional  support 
to  Horbaczewski's  view  that  uric  acid  comes  from  degenera- 
tion of  leucocytes,  and  is  formed  from  their  nuclein. 

The  opponents  of  Horbaczewski's  views  have  shown 
that  a  well-marked  digestive  leucocytosis  may  occur  after 
a  diet  of  egg  white,  or  even  after  a  non-nitrogenous  meal, 
and  yet  there  is  no  rise  in  uric  acid  excretion.  Moreover, 
it  has  been  shown  that  the  amount  of  disintegration  of 
the  leucocytes  could  be  measured  by  the  amount  of  phos- 
phoric acid  secreted,  for  this  substance  is  also  a  product 
of  the  breakdown  of  nuclein.  The  proportion  of  the  uric 
and  phosphoric  acids,  however,  does  not  always  run 
parallel,  and  in  a  case  of  leukaemia  recorded  by  Milroy 
and  Malcolm  there  was  even  a  diminution  of  phosphoric 
acid.  Kiihnau  in  an  extensive  and  careful  research  showed 
that  following  the  crisis  of  lumbar  pneumonia,  at  which 
period  there  is  an  increased  destruction  of  the  white  cells, 
there  is  an  increase  in  the  daily  amount  of  uric  acid  ex- 
creted. From  observations  that  he  made  in  various  other 
diseases  he  found  that  a  decrease  in  the  leucocyte  count 
is  generally  followed  by  a  corresponding  increase  in  the 

*  Arch.  /.  Exper.  Pathologie  und  Pharmakologie,  Bd.  xxii.,p.  306. 
f  Ceniralblatt   f.   allgemeine   Pathologie   und   pathologischen   Anatomic,    1896, 
vol.  vii.,  p.  820. 


Chap.  I]  URIC    AND    THYMIC    ACID.  9 

excretion  of  uric  acid,  an  increase  which  he  considers 
is  caused  by  the  increase  in  the  destruction  of  the  white 
corpuscles.  O.  K.  WiUiams*  has  made  a  series  of  obser- 
vations in  pulmonary  tuberculosis  in  order  to  ascertain 
whether  an  increase  of  the  white  cells  is  followed  by  an 
increase  in  the  amount  of  uric  acid  excreted,  and  in  order 
to  show  that  such  an  increase  in  the  excretion  of  uric  acid 
is  due  to  an  increase  in  the  destruction  of  the  white  cells, 
he  made  a  determination  of  the  amount  of  phosphoric  acid 
excreted  as  well  as  uric  acid.  He  found  as  a  result  of  his 
investigations  that  in  the  majority  of  cases  in  which  an 
increased  excretion  of  phosphoric  acid  follows  an  increase 
of  destruction  of  white  corpuscles  there  is  associated  with 
this  increase  a  corresponding  increase  in  the  amount  of 
uric  acid  excreted. 

Uric  acid  and  thymic  acid. — By  the  splitting  up  of 
the  nucleins,  as  shown  by  Schmoll,  there  are  produced  :  {a) 
albumin,  and  {b)  the  nucleic  acid  group  :    thus — 

Nucleins 


Albumin  Nucleic  acid 


Thymic  acid  Xanthin  bases  or  purin  bases 

Uric  acid. 

The  nucleins  when  split  up  by  digestion  yield  simple 
albumin  and  nucleic  acid,  nucleic  acid  again  yielding 
thymic  acid  and  the  xanthin  bases.  Since  nucleic  acid, 
by  splitting  up,  yields  ultimately  uric  acid  and  thymic 
acid,  Minkowski  and  Kossel  advanced  the  hypothesis  that 
thymic  acid  is  the  substance  which,  combined  with  uric 
acid,  renders  the  latter  soluble,  and  that  this  combination 
cannot  readily  be  broken  up,  so  that  uric  acid  cannot  be 
recovered,  after  it  has  once  combined  with  thymic  acid, 
without  prolonged  boiling.      According  to  this  view  uric 

*  Lancet,  1903. 


10  GOUT :    PATHOLOGY.  [Part  i. 

acid,  as  soon  as  formed,  combines  with  thymic  acid.  In 
this  combination  it  circulates  in  the  blood  and  is  excreted 
by  the  kidneys,  partly  in  its  combined  state  and  partly 
after  the  breaking  up  of  this  combination.  Regarded  in 
this  light,  the  presence  of  uric  acid  in  gouty  fluids  and 
tissues  is  explained  by  the  absence  of  a  proper  proportion 
of  thymic  acid  combined  with  it  and  keeping  it  in  solu- 
tion. In  the  normal  state  uric  acid  is  produced  by  the 
oxidation  of  the  purin  bases  ;  in  the  gouty  state  the  com- 
bination with  thymic  acid  does  not  take  place. 

It  is  erroneous  to  regard  the  amount  of  uric  acid  in  the 
urine  as  synonymous  with  the  amount  produced  in  the 
body.  The  uric  acid  produced  in  metabolism  in  great 
measure  leaves  the  body  by  the  urine,  but  all  of  it  certainly 
does  not.  Some  may  be  retained  within  the  body  for  a 
time  (an  exaggeration  of  this  is  seen  in  gouty  concre- 
tions) ;  some  may  be  further  oxidised  and  converted  into 
urea  and  simpler  products  ;  some  may  enter  into  combina- 
tion with  other  organic  substances,  lose  its  identity,  and 
the  nitrogen  ultimately  leave  the  organism,  not  only  as 
uric  acid,  but  in  other  forms  also.  Kossel  and  Goto^  have 
shown  that  uric  acid,  like  other  purin  substances,  will 
form  in  vitro  loose  combinations  with  nucleic  acid,  and  in 
this  way  uric  acid  may  be  held  in  solution.  It  is  thus 
possible  that  the  action  of  nucleic  acid  and  its  compounds 
in  the  body  may  be  a  factor  in  determining  the  solubility  of 
uric  acid  there. 

The  pupin  bodies. — The  term  "  purin  "  has  been 
applied  by  E.  Fischer  to  a  nucleus  QN4,  and  all  bodies 
constructed  upon  such  a  base  are  included  under  this 
name.  The  purin  bodies  of  ordinary  occurrence  are  Hypo- 
xanthin  (C6H4N4O),  Xanthin  (QH^N  OJ,  Uric  Acid 
(C5H4NA),  Guanin  (CsH.N^O),  Adenin  (QH^N^),  Caffein 
(QHN402(CH3)3),  and  Theobromin  (QH2N40,'(CH3)2).  By 
some  writers   these   bodies   are   styled  alloxur  bodies   (or 

•  Stizungst.   Gesellsch.   gesammt.   Naturwissensch.  Marburg,  1900,   April   6th. 


Chap,  f]  THE     PURIN      BODIES.  II 

bases),  or  xanthin  bodies.  Kossel  was  the  first  to  estab- 
lish the  close  chemical  connection  between  nucleins  and 
the  xanthin  or  purin  bodies. 

The  purin  bodies  exist  either  in  a  free  state  or  com- 
bined with  albumin  in  the  form  of  nucleic  acid.  Hypo- 
xanthin  and  xanthin  occur  in  muscle  extracts.  Adenin 
is  yielded  chiefly  by  the  decomposition  of  the  nucleic  acid 
present  in  thymus,  and  guanin  by  the  nuclein  prepared 
from  pancreas. 

Uric  acid  and  the  purin  group  of  bodies  are  derived 
from  the  "  nucleins  "  or  materials  of  which  the  cell-nuclei 
consist.  The  breaking-up  of  these  nuclei  gives  rise  to  uric 
acid  and  the  purin  or  alloxur  bodies.  Now,  it  is  clear 
that  two  possible  origins  of  these  substances  as  met  with 
in  the  body  are  thus  conceivable  :  viz.,  from  the  nuclei 
of  the  cells  of  the  living  body  itself,  and  from  those  of  the 
animal  and  vegetable  matter  consumed  as  food.  Both 
of  these  may  give  rise  to  uric  acid  in  the  system,  the  food- 
nuclei  causing  what  is  known  as  the  exogenous,  the  body 
cells  the  endogenous,  supply.  An  excessive  supply  of 
nuclear  products  may  thus  arise  from  the  consumption  of 
kinds  of  food  rich  in  these  elements,  or  from  some  perverted 
metabolism  of  the  body-cells. 

The  daily  "  wear  and  tear  "  or  metabolism  of  cell  con- 
stituents leads  to  the  production  of  a  certain  amount  of 
purin  bodies.  Whether  this  occurs  in  the  vegetable,  animal, 
or  human  organism,  these  substances  constitute  the  en- 
dogenous purins  of  the  excreta.  When  tissues  contain- 
ing nucleins  or  free  purins  are  eaten  by  lower  animals  or 
by  man,  the  endogenous  purins  of  the  food  ingested 
become  exogenous  to  the  system  which  absorbs  them. 
As  endogenous  purins  are  practically  waste  products 
on  their  way  to  excretion,  so  when  they  become  exoge- 
nous to  another  organism,  they  have  little  nutritive  value, 
and  demand  early  and  rapid  elimination.  This  is  gener- 
ally effected  by  the  oxidation  of  the  oxy-purins,  hypoxanthin 


12  GOUT:    PAtHOLOGY.  tPARx  i. 

and  xanthin,  to  uric  acid,  and  then  the  purin  ring  or  chain 
in  tlie  uric  acid  is  in  the  Hver  partially  split  off  and  a  por- 
tion of  the  uric  acid  excreted  as  urea. 

All  purins  are  therefore  primarily  of  an  endogenous 
origin.  What,  then,  are  the  sources  of  the  endogenous 
purins  ?  At  the  moment  the  lack  of  definite  evidence  pre- 
cludes a  definite  reply,  but  for  purposes  of  discussion  we 
may  perhaps  formulate  their  probable  sources  with  some 
show  of  precision,  and  thus  consider  them  as  arising  (i) 
by  synthesis  ;  (2)  from  the  destruction  of  leucocytes  ;  (3) 
from  the  breaking-up  of  nucleo-proteids  during  cell  pro- 
cesses. 

Endogrenous  purins. — The  sources  of  endogenous  purins 
are  probably  numerous,  and  the  quantities  derived  from 
each  may  vary  with  the  hourly  activities  and  daily  needs. 
The  endogenous  purin  is  partly  derived  from  leucocytes, 
but  mostly  from  the  cell  changes  which  result  in  the  main- 
tenance of  bodily  functions.  Hence,  as  the  cell-nucleus 
is  the  dominating  factor  in  metabolism,  the  cleavage  of 
cell  nucleins  may  incite  the  decomposition  of  proteid 
matter.  It  is  possible  that  the  endogenous  urinary  purin 
represents  about  one-half  of  the  total  endogenous  purin 
produced,  and  that  the  latter  quantity  indicates  the  extent 
of  metabolic  processes  more  completely  than  any  other 
factors  at  present  available. 

In  regard  to  normal  leucolysis  as  a  probable  source  of 
endogenous  purins,  it  is  only  possible  for  this  condition 
to  contribute  a  very  small  proportion  of  the  total  out- 
put. True  it  is  that  in  leukaemia  the  enormous  increase  of 
leucocytes  is  accompanied  by  an  increased  output  of  uric 
acid  ;  but  it  is  known  that  in  leucopenia,  even  when  the 
leucocytes  are  lowered  to  1500  to  3000  per  cm.,  the  uric 
acid  or  purin  excretion  is  practically  unaltered.  To  pro- 
duce one  gram  of  purin  bodies  large  numbers  of  leucocytes 
are  necessary — numbers  out  of  all  proportion  to  the  leu- 
cocytosis   of   febrile   and   acute   inflammatory   conditions ; 


CHXP.  I]  ENDOGENOUS   PURINS.  13 

so  that,  while  we  may  include  leucolysis  in  a  list  of  the 
sources  of  endogenous  purin  and  uric  acid,  it  cannot  be 
considered  as  an  important  factor. 

So  far  as  experimental  results  can  suggest  normal 
action,  one  portion  of  the  total  endogenous  purins  is  broken 
down  to  urea  and  the  remainder  excreted  as  uric  acid. 
Abnormal  endogenous  purin  metabolism  may,  therefore, 
consist  in  an  increased  production  with  excessive  or  dimin- 
ished destruction,  or  in  decreased  production  with  exces- 
sive or  diminished  destruction. 

It  is  quite  possible  that  the  conception  of  the  existence 
of  the  quadriurates  will  have  to  be  abandoned,  and  that 
it  will  be  necessary  to  substitute  therefor  the  view  of  uric 
acid  organic  combinations  as  a  necessity  for  their  normal 
circulation.  If  we  allow  such  a  possibility,  then  some 
idea  may  be  gained  of  the  resultant  effect  of  the  presence 
of  the  imperfect  metabolites  in  the  tissues,  and  our  thera- 
peutics be  directed  to  the  restoration  of  normal  meta- 
bolised bodies,  rather  than  to  the  attempted  solution  and 
elimination  of  uric  acid. 

The  destruction  of  uric  acid,  according  to  recent  work 
upon  the  subject,  takes  place  mainly  in  the  liver  ;  but 
Wiener,  working  with  organ  extracts,  showed  that  such 
prepared  from  liver,  kidneys,  and  muscles  were  able  to 
decompose  uric  acid.  If  his  methods  were  reliable  and 
his  experiments  correspond  to  intra-vitam  processes,  the 
tissues  generally  may  share  in  the  uric  acid  destruction. 
But  the  role  of  the  latter  must  be  small  compared  with 
that  of  the  liver,  and  to  this  conclusion  the  later  experi- 
ments of  Burian  and  Schur  distinctly  point.  Probably, 
therefore,  the  exogenous  purin  remainder  is  decomposed 
chiefly  in  the  liver,  perhaps  partly  in  the  tissues,  and  finally 
excreted  as  urea,  or  as  bodies  intermediate. 

Exogenous  purins. — Every  healthy  adult  excretes  a 
certain  amount  of  purin  substances  which  is  independent 
of   his    diet  ;     this    is    the    result    of    tissue    metabolism 


14 


GOUT:    PATHOLOGY. 


[Part  I. 


(endogenous  urinary  purin).  Its  amount  may  be  directly 
estimated  by  examining  the  urine  after  a  diet  of  substances 
which  are  practically  free  from  purin  compounds  ;  such 
articles  of  diet  are  milk,  cheese,  white  bread,  potatoes, 
rice,  green  vegetables,  etc.  This  Aiethod  of  examination 
is  much  better  than  that  of  analysing  the  urine  during 
hunger.  In  inanition  the  upset  produced  in  metabolism 
generally  is  sure  to  give  untrustworthy  results.  When  a 
man  takes  his  ordinary  diet,  which  includes  articles  con- 
taining nuclein,  or  purin  compounds,  the  amount  of  urinary 
purin  is  increased  by  a  part  of  the  purin  derived  from  his 
diet,  and  this  increase  may  be  termed  "  exogenous  urinary 
purin."  The  "  nutrition  purin  "  does  not  pass  wholly  into 
the  urine  ;  a  certain  fraction  remains  in  the  organism,  the 
purin  double  ring  being  broken  down.  The  amount  of 
the  remainder  (exogenous  urinary  purin)  differs  for  differ- 
ent forms  of  food,  and  is  but  little  affected  by  the  indivi- 
duality of  the  subject  of  the  experiment.  The  following 
table  by  Burian  and  Schur  *  gives  some  of  the  results 
obtained  by  them  : — 

TABLE    I. 


Diet. 

Total  percentage  of 

purin  substances 

in  diet. 

Percentage  of  exo- 
genous urinary 
purin. 

Beef 

Coffee 

Calf's  liver 

Calf's  spleen       .... 
Calf's  thymus     .... 

0.06 
0.20 
0.  12 
0. 16 
0.40 

0.030 
0.075 
0.060 
0.080 
0. 100 

By  subtracting  the  exogenous  from  the  total  urinary 
purin,  the  endogenous  urinary  purin  is  obtained,  and  the 
numbers  come  out  closely  with  the  results  obtained  by 
direct  estimation  ;  it  varies  in  the  majority  of  people  from 
0.1  to  0.2  grammes  daily,  but  values  both  higher  and 
lower  than  these  were  obtained. 


Pfliiger's  Arch.,  1900,  vol.  Ixxx.,  pp._24i-343. 


Chap,  I.]  EXOGENOUS    PURINS.  15 

In  white  bread,  rice,  eggs,  salad  and  cauliflower,  Burian 
and  Schur  found  no  xanthins.  By  use  of  these  foods  they 
determined  the  endogenous  urinary  purins  in  a  number 
of  cases,  and  obtained  results  of  individual  constancy. 
When  the  endogenous  urinary  purin  was  estimated,  and 
the  amount  of  the  food  purin  also  known,  they  were  able 
to  explain  the  relation  of  the  food  purin  to  the  urinary 
purin,  and  knowing  the  amount  of  the  food  purin  and  the 
total  urinary  purin,  they  were  able  to  calculate  the  quan- 
tity of  endogenous  urinary  purin.  To  obtain  the  average 
amount  of  endogenous  purin  excretion.  Walker  Hall  em- 
ployed a  fixed  purin-free  diet,  consisting  of  eggs,  bread, 
milk,  cheese,  butter,  rice,  and  sugar.  Neither  tea,  coffee, 
nor  beer  was  taken.  His  results,  which  are  in  accordance 
with  those  of  Burian  and  Schur,  show  that  upon  an  almost 
purin-free  diet  an  average  of  0.1623  grammes  purin-N.  per 
day  was  excreted,  or  0.4869  grammes  in  terms  of  uric  acid 
and  xanthin  bases. 

The  further  results  of  Walker  Hall's  experiments  after 
the  consumption  of  purin-containing  foods  show  that :  (i) 
with  chicken  54.4  per  cent,  of  the  food  purin  appears  in 
the  urine  as  exogenous  purin  ;  (2)  with  plaice  58.7  per  cent. 
of  the  food  purin  appears  in  the  urine  as  exogenous  purin  ; 
and  (3)  with  beef  47.4  per  cent,  of  the  food  purin  appears 
in  the  urine  as  exogenous  purin.  It  thus  appears  probable 
that,  allowing  for  the  variations  which  occur  in  different 
animals,  as  well  as  in  separate  species,  the  system  excretes 
in  the  urine  (within  forty-eight  hours)  about  one-half  of 
the  fish,  fowl,  or  beef  purins  contained  in  the  food.  An  addi- 
tional experiment,  made  to  determine  the  exogenous  purins 
after  ingestion  of  haricot  beans,  showed  that  55  per  cent. 
of  the  food  purin  appeared  in  the  urine  as  exogenous  purin. 

Walker  Hall's  results,  together  with  those  of  Burian 
and  Schur,  show  that  roughly  50  per  cent,  of  the  purin 
contained  in  the  food  reappears  in  the  urine  ;  but  such 
amount   can    only  be   taken  as  a  broad   average,  and  is 


i6  GOUT:    PATHOLOGY.  [part  i. 

applicable  only  to  healthy  individuals  upon  perfectly  assimi- 
lable diets.  All  foods  containing  purin  bodies  thus  appear 
to  increase  the  excretion  of  uric  acid  and  the  xanthins. 
On  the  other  hand,  the  consumption  of  milk,  a  purin-free 
food,  was  found  by  Burian  and  Schur  to  result  in  a  very 
low  uric  acid  excretion.  Amongst  foodstuffs,  the  purin 
bodies,  with  the  exception  of  uric  acid,  are  widely  distri- 
buted. They  exist  in  all  forms  of  meat  extracts,  in  the 
flesh  meats  of  ordinary  consumption,  and  in  larger  quanti- 
ties in  the  glandular  organs — thymus,  pancreas,  etc.  In 
lesser  amount  they  occur  in  many  vegetables,  as  oats, 
potato,  and  sugar  beet. 

So  far  only  that  portion  of  the  food-purin  has  been 
considered  which,  after  oxidation  to  higher  forms  in  the 
tissues  or  liver,  or  in  both,  appears  in  the  urine  in  quanti- 
ties representing  about  half  of  the  amount  ingested.  The 
next  point  to  consider  is  what  is  the  fate  of  the  other  50 
per  cent.  ?  Swain  considers  that  allantoin  may  be  looked 
upon  as  an  intermediary  product  between  uric  acid  and 
urea,  and  that  under  ordinary  circumstances  about  50  per 
cent,  of  the  uric  acid  produced  is  almost  completely  oxi- 
dised to  urea,  but  that  when  the  metabolic  organs  are 
unable  fully  to  decompose  the  purin  radical  more  allantoin 
and  less  urea  appear  in  the  urine. 

It  may  therefore  be  inferred,  according  to  the  views 
just  enunciated,  that  uric  acid  is  now  more  generally  re- 
garded as  an  intermediary  metabolic  product,  and  that  its 
appearance  in  the  urine  is  due  to  incomplete  decomposition. 

It  will  be  seen  that  the  exogenous  nucleins  simply  pass 
through  the  body.  Their  phosphorus  may  be  retained  for 
synthetic  or  organic  purposes,  and  the  small  amount  of 
albumin  they  contain  may  be  used  up  in  the  tissues  ;  but 
their  purin  contents  are  not  employed  in  the  synthesis  of 
cell  nucleins.  Through  some  decomposition  of  the  purin 
ring,  a  definite  proportion  of  the  purin  bodies  is  liberated, 
oxidised,   and   excreted   as  uric  acid,   and  the  remainder 


Chap,  ij  THE    PURIN    BODIES.  17 

eliminated  as  urea  or  as  bodies  intermediate.  The  results 
of  Soetbeer  and  Ibrahim  also  support  the  statement  that 
50  per  cent,  of  the  exogenous  purin  bodies  are  oxidised  to 
uric  acid,  and  50  per  cent,  are  further  broken  down  and 
excreted  as  urea  or  intermediate  bodies.  Since  the  definite 
division  of  purin  bodies  into  "endogenous"  and  "exoge- 
nous," too  little  time  has  elapsed  for  the  record  of  many 
observations  ;  but  from  the  studies  of  Reach,  Kaufmann, 
Vogt,  and  Chalmers  Watson,  it  may  be  shown  that  in  gout 
exogenous  nuclein  is  more  slowly  excreted  than  in  health, 
and  that  in  some  cases  there  is  distinct  retention. 

In  leuksemia  the  formation  of  endogenous  purin  is  ex- 
cessive, and  the  urine  contains  very  large  quantities  of  uric 
acid.  In  this  case  the  endogenous  purins  are  probably 
diminished  by  the  anaemia  and  its  consequent  tissue  mal- 
nutrition, and  augmented  by  the  formation  and  destruc- 
tion of  enormous  numbers  of  leucocytes.  Chalmers  Watson 
has  recorded  the  appearance  of  a  peculiar  type  of  white  cell, 
large  in  size  {15  yu,),  with  a  large  oval  or  horseshoe-shaped 
nucleus,  poor  in  chromatin,  the  protoplasm  vacuolated  and 
imperfectly  stained.  These  cells  could  be  readily  differen- 
tiated from  the  ordinary  finely  granular  oxyphile  leucocyte, 
and  also  from  the  lymphocyte  ;  in  form  and  general  ap- 
pearance they  resemble  degenerated  myelocytes.  During 
the  acute  attack  these  cells  were  considerably  increased  in 
number,  and  their  presence  suggested  the  possibility  of 
their  having  an  important  relationship  to  the  alterations 
in  the  uric  acid  and  phosphoric  acid  excretion  observed  in 
the  same  case. 

Purin  bodies  and  blood  pressure. — Walker  Hall's 
experiments  upon  the  effect  of  the  purin  bodies  showed 
that  they  did  not  lead  to  any  alterations  in  the  general 
blood-pressure.  As  to  the  form  in  which  uric  acid  circu- 
lates in  the  tissue-fluids,  much  conjecture  exists  ;  the 
quadriurate  may  occur  in  some  parts  of  the  blood-stream 
but  as  the  presence  of  these  exogenous  purins  in  the  blood- 
c 


i8  GOUT :    PATHOLOGY.  [px«t  i, 

stream  in  the  form  of  uric  acid  and  xanthin-bases  is  not 
indicated  by  the  usual  tests  for  those  substances,  it  is 
probable  that  they  exist  in  the  blood  in  some  loose  organic 
combination.  A  considerable  amount  of  evidence  has 
lately  accumulated,  which  suggests  that  the  purin-bases, 
mono-  and  di-oxypurin  alike  with  the  tri-oxypurin,  uric 
acid,  exist  in  the  blood-stream  in  combination  with  a  com- 
plex organic  body  ;  hence  the  views  as  to  different  forms 
of  circulating  inorganic  urate  combinations  may  ultimately 
require  revision. 

George  Oliver  has  shed  very  clear  light  upon  some  of 
the  processes  which  take  place  in  the  lymphatic  and  tissue 
spaces.  Amongst  other  results,  he  shows  that  the  purin 
bodies  increase  the  exudation  of  lymph,  and  consequently 
affect  the  lymph  flow.  Now,  it  is  beyond  question  that 
uric  acid  and  the  purin  bases  are  present  in  excess  in  the 
blood  and  tissue  spaces  of  the  gouty  individual,  so  that  we 
may  appreciate  Oliver's  contention  that  the  hypertonic 
circulatory  conditions  in  the  patient  affected  with  gout  are 
associated  with  persistently  increased  lymph  pressure,  the 
consequent  depression  of  metabolic  processes,  and  the 
resultant  increased  arterial  pressure  with  its  usual  vascular 
changes. 

Pupin  bodies  and  absorption. — Walker  Hall  has 
shown  that  the  faeces  of  gouty  patients  frequently  contain 
increased  quantities  of  fat,  and  the  percentage  of  un- 
absorbed  nitrogen  rises  from  about  i  per  cent,  to  2.5  per 
cent.  Further,  the  researches  of  His,  Von  Noorden,  and 
Kaufmann  and  Mohr  show  that  the  powers  of  absorption 
diminish  as  the  disease  progresses.  This  increase  of  nitro- 
gen, however,  is  not  due  to  food-nitrogen  alone,  for  it  may 
arise  from  augmented  quantities  of  digestive  secretions, 
from  excessive  epithelial  desquamation,  or  as  a  result  of 
intestinal  putrefaction.  The  actual  loss  of  unabsorbed 
food  is  of  less  importance  than  the  evident  cellular  defi- 
ciency which  may  permit  the  passage  of  extrinsic  toxing 


Chap.  I.]  THE   PURIN    BODIES.  19 

or  imperfectly  digested  substances  into  the  general  tissues. 
An  estimate  of  the  exact  extent  of  intestinal  derangement 
is  hence  of  more  value  than  a  determination  of  the  quan- 
tity of  unabsorbed  proteid.  The  amount  of  shed  epi- 
thelium, and  perhaps  of  certain  intestinal  juices  and  bac- 
terial products,  may  be  better  appraised  by  investigations 
into  the  purins  of  the  faeces,  since  these  in  part  represent 
the  nuclein-contents  of  the  desquamated  cells.  Results 
show  that  the  healthy  intestinal  epithelium  manifests 
certain  selective  powers,  and  that  the  absorbed  food- 
nucleins  depend  either  upon  the  individual  nuclein-base  or 
upon  the  constitution  of  the  particular  nucleo-proteid. 

Vogt  compared  the  results  of  rich  purin-holding  food 
upon  a  gouty  patient  and  a  healthy  individual  at  the  same 
time.  The  gouty  patient  showed  retention,  and  delayed 
excretion  of  purin  bodies.  These  studies  confirm  clinical 
experiences,  and  there  is  thus  little  doubt  that  the  gouty 
individual  does  not  well  metabolise  exogenous  purins. 

The  presence  of  large  amounts  of  purin  bodies  in  the 
tissue  fluids  produces  no  ill  effects  if  the  kidney  is  normal  ; 
for  instance,  gouty  symptoms  do  not  always  accompany 
rich  nuclein-intake,  nor  appear  in  leukaemic  patients. 
The  molecular  concentration  of  the  blood  is  generally 
normal  ;  there  is  neither  distinct  leucocytosis,  altered  num- 
bers of  red  blood  corpuscles,  nor  change  in  the  haemo- 
globin coefficient. 

Croftan  examined  the  uric  acid-destroying  quotient  of 
the  liver,  kidney,  muscle,  blood,  and  spleen  after  the  re- 
moval of  these  tissues  from  the  body.  The  human  kidney 
appeared  to  destroy  more  uric  acid  than  the  liver,  and  the 
muscles  more  than  either  the  liver  or  kidney.  He  ascribes 
these  results  to  the  action  of  unorganised  soluble  ferments, 
and  considers  that  his  experiments  favour  the  renal  theory 
of  gout. 

Conclusions  concerning:  the  purin  bodies. — The 
most  recent  investigations  tend  to  show  that  uric  acid  is 


20  GOUT:    PATHOLOGY.  [part  i. 

in  no  sense  longer  to  be  regarded  as  a  product  of  the  im- 
perfect combustion  of  proteids  into  urea,  that  no  mere 
excess  of  nitrogenous  foods  as  such  is  capable  of  produc- 
ing it,  but  it  closely  depends  upon  the  amount  of  nucleins, 
purins,  and  the  alloxur  group  in  the  food.  Excess  of  nitro- 
genous food  has  been  shown  by  Burian,  Schur,  Horbac- 
zewski,  and  Minkowski  to  result  in  the  increase,  not  of  uric 
acid  and  the  urates,  but  of  urea  ;  while  by  the  administra- 
tion of  bodies  rich  in  nucleins  and  purins,  such  as  roe, 
sweetbread,  thyroid  extract,  etc.,  the  uric  acid  output 
could  be  increased  in  a  marked  degree.  Finally,  by  a  care- 
ful selection  of  nitrogenous  bodies  which  were  especially 
poor  in  nucleins  and  the  alloxur  group,  the  urea  could  be 
largely  increased  while  uric  acid  was  actually  diminished 
in  amount.  About  half  our  normal  output  is  probably 
due  to  this  source — the  exogenous  uric  acid. 

The  experiments  of  Minkowski,  in  which  by  ligating  the 
ureters  of  birds  he  succeeded  in  producing  an  accumulation 
of  urates  in  the  tissues,  resembling  tophi,  gave  rise  to  no 
other  gouty  or  lithsemic  symptom,  not  even  to  local  re- 
actions round  the  deposits,  and  only  such  toxic  symptoms 
as  were  due  to  the  retention  of  all  urinary  excreta.  Woods- 
Hutchinson  in  his  necropsies  at  the  London  Zoological 
Gardens  repeatedly  found  small  masses  of  urates  just  under 
the  surface  of  the  pericardium  and  the  peritoneum,  and 
even  upon  the  valves  of  the  heart  itself,  in  birds  and 
reptiles  without  giving  rise  to  any  symptoms  of  local 
irritation. 

During  a  gouty  attack  there  is  a  marked  increase  of 
phosphoric  acid  in  the  urine.  As  has  been  shown  by  Futcher, 
the  curve  of  uric  acid  output  runs  in  a  striking  parallel 
with  that  of  phosphoric  acid,  and  as  all  nucleins  are  com- 
posed of  a  phosphoric  acid  element,  nucleic  acid  united 
with  a  purin  or  adenin  base,  we  have  here  the  other  moiety 
of  the  nuclei  of  the  cells  which  have  been  destroj^ed  in 
the  toxic  process. 


Chap.  I]  ORIGIN     OF     URIC    ACID.  21 

Woods-Hutchinson,  in  an  interesting  paper,*  comes  to 
the  following  conclusions :  The  uric  acid  produced  in 
health  comes  exclusively  from  two  sources — the  larger 
moiety,  or  exogenous  uric  acid  of  Chittenden,  from  the 
nucleins  and  purin  bases  of  the  food  ;  the  smaller,  or  endo- 
genous moiety,  from  the  destructive  metabolism  of  the 
nucleins  of  the  body  tissues.  It  is  the  endogenous  moiety 
alone  which  is  increased  in  gout  and  lithsemia. 

The  uric  acid  of  gout,  like  the  phosphoric  acid  which 
invariably  accompanies  it,  is  merely  a  result  and  measure 
of  the  destructive  metabolism  of  the  nucleins  of  the  body 
cells,  chiefly  probably  of  the  leucocytes,  in  response  to  the 
invasion  of  poisons  or  toxins.  Parallel  examinations  of 
the  blood  and  urine  have,  however,  subsequently  shown 
that  leucocytosis  does  not  regularly  accompany  increased 
uric  acid  excretion,  and  Hutchison  and  Macleod  have  re- 
cently reported  a  case  of  leucopenia  in  which  the  alloxuric 
urinary  nitrogen  was  of  an  average  normal  amount.  Whilst 
we  may  thus  regard  leucocytic  destruction  as  one  source 
of  urinary  purin,  it  probably  does  not  play  such  an  im- 
portant role  as  was  formerly  thought. 

Attempts  have  lately  been  made  to  prove  that  the 
excretion  of  uric  acid  and  phosphoric  acid  (two  end  pro- 
ducts of  nuclear  disintegration)  go  hand  in  hand.  It  is 
very  doubtful  if  this  is  the  case.  Chalmers  Watson's 
observations  are  strongly  opposed  to  this  view.  It  is 
true  that  uric  acid  and  phosphoric  acid  are  two  end  pro- 
ducts of  metabolism  of  the  nucleins,  but  it  must  be  remem- 
bered that  the  uric  acid  formed  in  the  body  is  probably 
capable  of  further  and  rea<iy  transformation  into  urea, 
while  there  is  nothing  to  indicate  that  phosphoric  acid  can 
undergo  any  further  change  in  the  economy. 

The  origin  of  uric  acid  from  the  nuclein  of  the  food  is 
one  factor,  its  origin  from  the  nuclein  of  the  leucocytes 
is     another,    and,    as     pointed    out   by    Halliburton,    the 

*  Lancet,   1903. 


22  '   GOUT:    PATHOLOGY.  ipart  i, 

catabolism  of  the  nuclei  of  other  animal  cells,  such  as 
those  of  secreting  glands,  may  contribute  to  the  formation 
of  the  acid. 

Estimation  of  urinary  purins. — It  is  possible  to  ob- 
tain the  purins  in  the  form  of  a  silver-magnesium  precipi- 
tate, and,  by  measuring  the  amount  of  the  precipitate,  to 
ascertain  the  quantity  of  purins  present.  The  following 
is  a  description  of  the  process  devised  by  Walker  Hall. 
Two  solutions  are  necessary  : 

No.  I  solution.  No.  2  solution. 

Ludwig's    Magnesium*  Silver  Nitrate       .         .         i  gm. 

mixture     .         .         .     100  cc.  Ammonia  (strong)        .     100  cc. 

Ammonia  solution  20%     100  cc.  Talc       ....         5  gms. 

Talc      ....       10  gms.  Distilled  Water    .         .     100  cc. 

The  only  instrument  employed  is  the  "  purinometer." 
It  consists  essentially  of  three  parts  : — 

1.  A  closed  graduated  tube. 

2.  A  stop-cock,  with  a  bore  of  the  same  diameter  as 

the  upper  tube. 

3.  A  small  glass  reservoir  of  known  cubical  capacity. 
It  is  used  in  the  following  manner :  With  the  stop  at  a 

right  angle  to  the  tube,  urine  is  poured  in  up  to  90  cc.  The 
stop-cock  is  then  turned  parallel  with  the  tube,  and  the 
lower  chamber  and  the  bore  of  the  tap  become  filled  with 
the  urine  ;  20  cc.  of  solution  No.  i  are  then  added,  and  the 
precipitate  is  allowed  to  settle.  If  the  reagent  contains  no 
talc,  the  precipitated  phosphates  take  a  long  time  to  settle 
and  there  is  some  loss  of  uric  acid.  The  precipitate  of  phos- 
phates sinks  into  the  lower  chamber  of  the  purinometer, 
and  immediately  this  has  happened  the  tap  is  again  turned 
at  right  angles.  To  the  clear  fluid  now  remaining  in  the 
upper  tube,  solution  No.  2  is  added  to  make  the  total  fluid 
100  cc.     The  resultant  precipitate  consists  of  a  mixture  of 

*  This  mixture  consists  of — 

Magnesium  Chloride    .  .  .  .110  gms. 

Ammonium  Chloride  .  .  .  .      110     ,,  .t 

Ammonia  .....  250     „ 

'.    ■  Water  to   .  .  .  .  ■  .    1000  cc. 


Chap,  f.]  ESTIMATION   OF    PURINS.  23 

silver  chloride  and  silver-purin.  The  apparatus  is  then 
inclined  backwards  and  forwards  until  the  precipitate  is 
yellowish-white,  by  which  time  the  silver  chloride  will 
have  been  dissolved  out  by  the  excess  of  ammonia.  This 
can  be  readily  seen  by  comparison  with  the  white  phos- 
phate precipitate  in  the  lower  tube.  The  instrument 
is  now  allowed  to  stand  twenty-four  hours,  when  the  per- 
centage of  purin  may  be  read  off  at  the  upper  level  of  the 
precipitate. 

An  advantage  may  be  claimed  in  the  case  of  an  excess 
of  chlorides,  which  solution  No.  2  or  even  a  few  added 
drops  of  strong  amnjLonia  will  not  dissolve.  The  silver 
chloride  is  heavy  and  falls  rapidly  (within  a  minute),  whilst 
the  lighter  purin  precipitates  take  an  hour  or  so  to  settle. 
It  is  possible,  therefore,  to  allow  the  silver  chloride  to  fall, 
turn  the  stop-cock,  let  the  precipitate  pass  into  the  bore 
of  the  tap,  and  immediately  return  the  tap  to  a  right  angle. 
The  loss  of  any  purin-silver  is  by  this  means  exceedingly 
slight,  and  the  silver  chloride  excess  does  not  interfere  with 
the  estimation.  The  temperature  of  the  room  in  which 
the  estimations  are  made  should  be  between  10°  and  15°  C. 

By  use  of  the  centrifuge,  the  precipitates  become  con- 
stant in  a  few  minutes,  and  in  such  case  there  is  no  neces- 
sity for  the  addition  of  talc.  Where  such  apparatus 
exists,  the  convenience  of  the  method  is  increased  and 
the  results  are  more  regular.  A  graduated  centrifugalising 
tube  is,  however,  necessary. 

The  number  of  cc.  occupied  by  the  silver-purin  preci- 
pitate is  then  multiplied  by  a  factor  issued  with  the  purino- 
meter,  and  gives  the  percentage  amount  of  purin  nitrogen, 
which  can  be  converted,  if  desired,  into  terms  of  uric  acid. 


CHAPTER    II. 
THE   FORMATION   OF   URIC   ACID, 

View  that  uric  acid  is  formed  in  the  kidneys — Views  as  to  the 
association  of  gout  and  kidney  disease — View  that  the  liver  and 
spleen  produce  uric  acid — View  that  uric  acid  is  produced 
in  various  tissues — View  that  excess  of  uric  acid  is  the  result 
of  an  animal  diet. 

Uric  acid  and  the  kidneys. — Until  1847  it  was  sup- 
posed that  uric  acid  was  formed  in  the  kidneys  them- 
selves, as  up  to  that  time  none  had  ever  been  detected 
in  the  blood.  In  that  year  Sir  Alfred  Garrod  de- 
monstrated the  presence  of  uric  acid  in  the  blood  of  gouty 
subjects,  which  discovery  led  to  the  conclusion  that  uric 
acid  was  formed  in  certain  other  organs  and  tissues  of  the 
body,  and  was  merely  eliminated  by  the  kidneys.  The 
view  that  then  arose  was  that  the  uric  acid  eliminated  in 
the  urine  originated  in  the  system  by  the  metabolism  of 
the  nitrogenised  tissues,  and  was  then  thrown  out  by  the 
kidneys.  Sir  Alfred  Garrod  *  originally  held  this  view,  but 
in  later  years  he  came  to  the  conclusion  that  uric  acid 
is  produced  by  the  direct  action  of  the  kidneys  from  urea 
and  other  nitrogenised  bodies  contained  in  the  blood  and 
conveyed  to  the  kidneys.  From  the  experimental  evidence 
that  he  put  forward.  Sir  Alfred  Garrod  f  concluded  that 
the  presence  of  the  salt  of  uric  acid  in  the  blood  of  gouty 
subjects,  provided  it  is  not  introduced  via  the  alimentary 
canal,  must  be  accounted  for  by  absorption  into  the  blood 
from  the  kidneys  after  its  formation  in  those  organs,  the 

*  Trans,  of  the  Royal  Medical  and  Chirurgical  Society,   1848,  p.  93. 
t  Proceedings  of  the  Royal  Society,  1893,  pp.  482-484. 

24 


Chap,  it.]  URIC    ACID    AND    KIDNEYS.  25 

salt  being  changed  by  the  blood  from  ammonium  quadri- 
urate,  which  is  the  form  in  which  uric  acid  is  mainly  present 
in  the  kidneys,  to  sodium  quadriurate,  which  is  the  form 
in  which  uric  acid  first  appears  in  the  blood.  He  therefore 
held  that  uric  acid  is  normally  formed  in  the  kidneys,  and 
that  when  present  in  the  blood  it  is  a  result  of  its  having 
been  absorbed  after  formation  in  those  organs.  Kolisch* 
regards  the  kidneys  as  the  most  important  of  the  uric  acid- 
forming  organs.  Latham  considers  that  the  final  for- 
mation of  uric  acid  takes  place  in  the  kidneys,  where  it  is 
produced  by  the  conjugation  of  substances  manufactured 
in  the  liver,  and  conveyed  in  the  blood  to  the  kidneys. 

The  following  experimental  evidence  has  been  put  for- 
ward in  support  of  the  view  that  uric  acid  is  formed  in  the 
kidneys.  Zalesky  experimented  on  serpents,  who  elimi- 
nate all  their  urinary  nitrogen  as  uric  acid.  He  found  that 
after  removal  of  the  kidneys  of  serpents  they  lived  about 
as  long  a  time  as  when  the  ureters  were  tied,  and  that  after 
death  no  uratic  deposits  were  found  in  any  of  the  tissues. 
As  he  found,  after  ligaturing  the  ureters  of  other  serpents, 
that  uratic  deposits  were  to  be  seen  after  death  in  most  of 
the  organs  and  tissues,  he  concluded  that  the  kidneys  were 
the  producers  as  well  as  the  eliminators  of  uric  acid.  The 
following  experiments  also  seem  to  be  opposed  to  the  view 
that  the  kidneys,  with  regard  to  uric  acid,  merely  act  as 
filters,  which  separate  the  uric  acid  brought  to  them  in 
the  blood.  Sir  Alfred  Garrod  gave  from  fifteen  to  thirty 
grains  of  potassium  urate  daily,  and  similar  daily  doses  of 
sodium  urate,  without  producing  any  increase  of  uric  acid 
in  the  urine.  Wohler  and  Frerichs  found  that  the  adminis- 
tration of  potassium  and  sodium  urates  increased  the 
amount  of  urea,  but  did  not  augment  the  quantity  of  uric 
acid  in  the  urine.  Neubauer  found  that  the  administration 
of  large  quantities  of  uric  acid  to  rabbits,  either  by  the 
stomach  or  by  injection  into  the  veins,  was  followed  by  a 

*  Wien.   klin.    Woch.,   1895,   viii.,   p.   787. 


26  GOUT :    PATHOLOGY.  [parx  i. 

corresponding  increase  in  the  excretion  of  urea,  but  no  uric 
acid  was  discovered  in  the  urine. 

The  blood  of  the  renal  artery  is  much  richer  in  urea  than 
the  blood  of  the  renal  vein  ;  according  to  Picard,  in  the 
proportion  of  about  two  to  one,  according  to  Sir  Alfred 
Garrod  in  the  proportion  of  about  three  to  one.  From 
his  most  recent  observations,  Sir  Alfred  Garrod  concludes 
that  in  birds  and  other  uric  acid-excreting  animals  the 
metabolism  of  the  nitrogenised  tissues  is  exactly  the  same 
as  in  mammals.  He  believes  that  urea  is  the  ultimate 
product  of  this  metabolism,  and  that  the  uric  acid  is  a 
subsequent  product  of  the  union  of  urea  with  some  other 
principle  or  principles,  glycocine  probably  being  one  of 
them.  He  regards  the  kidney  as  the  organ  whose  function 
it  is  to  manufacture  uric  acid  from  the  nitrogenised  matters 
brought  to  it  in  the  blood,  and  considers  it  possible  that 
the  kidney  contains  different  cells — some  for  the  forma- 
tion of  urea,  and  some  for  the  formation  of  uric  acid — and 
that  the  ratio  between  the  two  may  vary  in  different  classes 
of  animals. 

P.  W.  Latham's  explanation  of  the  formation  of  uric 
acid  in  the  animal  economy  is  that  the  amido-bodies,  glyco- 
cine, taurine,  leucine,  and  tyrosine,  are  normally  converted 
in  the  liver  into  urea  ;  but  if  from  any  cause  the  meta- 
bolism of  glycocine  be  interrupted,  there  would  then  be 
present  in  the  liver  glycocine  and  urea,  which  would  produce 
hydantoic  acid,  and  then  hydantoin,  and  the  latter,  which 
is  freely  soluble,  would  pass  on  in  the  circulation  to  unite 
in  the  kidneys  with  urea  or  with  biuret  to  form  an  ammo- 
nium salt  of  uric  acid.  Therefore,  according  to  this  view, 
the  imperfect  metabolism  of  glycocine  is  the  primary  and 
essential  defect  in  connection  with  the  abnormal  forma- 
tion of  uric  acid  in  the  human  system. 

According  to  Latham,*  the  synthesis  of  uric  acid  from 
urea  and  glycocine  takes  place  in  the  following  steps  : 

*  Croonian  Lectures,  1886. 


Chap,  ii]  FORMATION  OF  URIC  ACID.  27 

1.  The   urea  and  glycocine   produce   hydantoic  acid — 
CH.,N,0  +  C2HJNH„)O.OH  =  C^H^N.O,  +  NH,. 

Urea  Glycocine  Hydantoic  acid 

2.  The  hydantoic  acid  becomes  dehydrated,  and  forms 
hydantoin-      c^H^N^O,  =  C,H,N,0,  +  H,0. 

Hydantoic  acid  Hydantoin 

3.  From  more  of  the  urea  biuret  is  produced — 

2  CH.N^O  =  CjH.NjO^  +  NH3. 

Urea  Biuret 

4.  By  combination  of  hydantoin  and  biuret,  uric  acid 
is  produced  — 

C,H^N,0,  +  C.H.NjO^  =  C^H.N.Oa  +  N  H,  +  H,0 

Hydantoin  Biuret  Uric  acid 

The  production  of  uric  acid  from  urea  and  glycocine 
may  be  shown  in  a  single  equation  as  follows  : — 
3  CH^N^O  +  C2H,(NH,)O.OH  =  C^H.N.Oa  +  3  NH3  +  2  H,0. 

Urea  Glycocine  Uric  acid 

Facts  supporting"  the  view  that  upie  acid  is  formed 
from  urea  and  glycocine. — There  are  several  reasons 
for  believing  that  uric  acid  may  be  formed  from  urea  and 
glycocine  in  the  living  organism.  Horbaczewski  produced 
uric  acid  by  the  interaction  of  urea  and  glycocine,  and 
this  result  was  confirmed  by  Latham.  Glycocine  is  cer- 
tainly formed  in  the  human  body,  and  probably  is  one  of 
the  antecedents  of  urea,  for  in  man,  glycocholic  acid,  a 
compound  of  glycocine  and  cholic  acid,  passes  in  the  bile 
into  the  intestine,  and  having  served  its  purpose,  and  its 
constituents  having  been  set  free,  the  glycocine,  together 
with  the  other  amido-bodies,  taurine,  leucine,  and  tyrosine, 
pass  in  the  portal  blood  to  the  liver,  and  probably  in  the 
hepatic  cells  are  converted,  or  mainly  converted,  into 
urea. 

That  glycocine  is  concerned  in  the  production  of  uric 
acid  is  somewhat  probable  from  the  fact  that  in  the  carni- 
vora,  whose  urine  contains  little  or  no  uric  acid,  the  bile 
contains   no   glycocholic   but   only   taurochohc   acid,    and 


28  GOUT:    PATHOLOGY.  [part  i. 

therefore  yields  no  glycocine.  The  experiments  of  Hahn, 
Massen,  Nencki,  and  Pawlow  also  support  the  view  that 
glycocine  is  concerned  in  the  formation  of  uric  acid.  They 
shut  the  livers  of  dogs  almost  completely  off  from  the 
general  circulation  by  diverting  the  portal  circulation  into 
the  inferior  vena  cava,  and  so  caused  an  increased  amount 
of  glycocine  to  be  sent  to  the  kidneys  by  preventing  its 
conversion  into  urea  in  the  liver.  They  found  that,  although 
the  dogs  passed  less  urea  (the  nitrogen  being  mainly  elimi- 
nated as  ammonium  carbamate),  the  uric  acid  voided  was 
considerably  increased.  Latham  *  believes  that  if  an  ex- 
cessive amount  of  nitrogenous  material  is  introduced  into 
the  portal  circulation,  the  portion  which  is  least  readily 
acted  upon  is  the  glycocine,  the  presence  of  which  promotes 
the  formation  of  uric  acid.  He  considers  that  the  primary 
defect  in  gout  consists  in  the  imperfect  metabolism  of 
glycocine. 

Uric  acid  formation  and  liver  disease. — If  uric  acid 
be  formed  in  the  kidneys  from  urea  and  glycocine  brought 
from  the  liver,  it  can  be  readily  understood  that  altera- 
tions in  the  metabolism  of  the  liver  must  necessarily  affect 
the  formation  and  excretion  of  uric  acid.  This  would 
explain  why  liver  trouble  of  some  kind  or  another  is  so  com- 
monly associated  with  gouty  dyspepsia,  and  also  renders 
intelligible  the  fact  that  several  observers  have  been  un- 
able to  dissociate  the  connection  between  liver  troubles 
and  gout,  and  have  therefore  attributed  the  formation  of 
uric  acid  to  the  liver.  For  instance,  Murchison  considered 
that  gout  is  an  hereditary  disease  by  virtue  of  the  transmis- 
sion by  parents  to  their  offspring  of  a  defective  power  of 
the  liver,  in  consequence  of  which  its  functions  are  deranged 
with  unusual  facility  ;  as  a  result  of  this  derangement 
of  the  liver  the  metabolism  of  the  albumen  is  to  a  great 
extent  arrested  at  the  stage  of  uric  acid  formation,  instead 
of  going  on  to  the  final  stage  of  urea  formation.     George 

*  Loc  cit. 


c„Ar,  11.]        KIDNEY  AFFECTIONS  AND    GOUT.  29 

Harley  considered  that  a  strong  relationship  existed  be- 
tween gout  and  hepatic  derangements.  Sir  Dyce  Duck- 
worth is  of  opinion  that  "  the  hver  is  the  organ  in  which 
in  health  uric  acid  is  chiefly  formed,  and  it  is  probably 
to  derangement  of  function  in  this  gland  that  we  must 
look  for  over-production  of  this  substance."  All  these 
views  are  rendered  equally,  if  not  more,  intelligible  by 
regarding  the  liver  as  the  seat  of  production  of  the  ante- 
cedents of  uric  acid  (urea  and  glycocine),  the  final  conjuga- 
tion of  those  bodies  taking  place  elsewhere. 

Association  of  kidney  affections  with  gfout,  —  An 
interesting  point  to  consider  is  whether  gout  ever  occurs 
without  preceding  kidney  mischief  of  some  kind  or  other. 
That  is,  whether,  if  the  kidneys  remain  sound,  it  is  possible 
for  such  an  accumulation  of  uric  acid  to  occur  in  the  system 
as  to  produce  an  attack  of  gout.  We  will  first  ascertain 
whether  there  is  any  evidence  that  an  affection  of  the 
kidneys  (functional  or  organic)  is  associated  with  or  pre- 
cedes gout.  To  begin  with,  it  is  time  that  the  old  idea 
should  be  abandoned  that  the  healthy  kidneys  can  only 
eliminate  a  certain  amount  of  uric  acid.  That  the  healthy 
kidneys  are  capable  of  separating  from  the  blood  and  ex- 
creting large  quantities  of  uric  acid  is  shown  by  the  observa- 
tions of  Laache,  Bartels,  Stadthagen,  and  Bohland  and 
Scherz,  on  the  excretion  of  uric  acid  in  cases  of  leukaemia. 
In  this  disease  the  blood  is  laden  with  uric  acid,  and  all 
these  observers  found  a  greatly  increased  daily  excretion 
of  uric  acid,  varying  from  twice  to  over  six  times  the  normal 
amount.  This  large  excretion  of  uric  acid  by  the  kidneys 
shows  that  urates  do  not  themselves  cause  damage  to 
kidney  tissues. 

Sir  Alfred  Garrod,  Sir  William  Roberts,  and  Levison 
all  attribute  the  accumulation  of  uric  acid  in  the  blood 
of  gouty  persons  to  deficient  excretion  rather  than  to 
increased  production.  Sir  Alfred  Garrod  holds  the  view 
that  among  the  causes  exciting  a  gouty  fit  is  a  functional 


30  GOUT:    PATHOLOGY.  [Part  i. 

failure  of  eliminating  power  for  uric  acid  on  the  part  of 
the  kidneys.  He  also  considers  that  this  early  functional 
failure  is  followed  in  cases  of  chronic  gout  by  structural 
kidney  disease.  His  view  is  that  the  uric  acid  present 
in  the  blood  of  gout  is  formed  in  the  kidneys,  and  is  ab- 
sorbed from  them  into  the  blood.  This  view  is  quite  com- 
patible with  the  theory  that  a  defective  capacity  of  the 
kidneys  for  the  excretion  of  uric  acid  is  the  primary  patho- 
logical cause  of  gout.  Levison  *  states  that  gout  is  not 
accompanied  by  leucocytosis,  and  therefore  the  nuclein 
of  leucocytes  is  not  available  for  the  production  of  uric 
acid.  He  considers  that  gout  cannot  be  developed  unless 
a  primary  renal  lesion  is  present,  and  that  this  is  almost 
invariably  of  the  nature  of  an  interstitial  change.  Vogel  "f" 
estimated,  in  three  cases  of  chronic  gout,  the  intake  of 
nitrogen  by  analysis  of  the  food  and  the  output  of  nitrogen 
in  the  urine  and  fseces.  He  found  that  there  was  a  nitrogen 
retention  greatly  in  excess  of  what  could  be  attributed 
to  a  retention  of  uric  acid.  Vogel  states  that  his  patients 
behaved,  in  this  respect,  like  sufferers  from  renal  disease, 
although  the  clinical  signs  of  granular  kidney  mischief 
were  wanting  in  all  the  cases.  In  connection  with  this, 
it  must  be  borne  in  mind  that  the  absence  of  the  clinical 
signs  of  disease  of  the  kidneys  does  not  necessarily  imply 
integrity  of  those  organs. 

Association  of  renal  disease  with  the  presence  of 
uric  acid  in  the  blood,  and  with  uratic  deposits  in 
the  joints. — Von  Jaksch  found  considerable  quantities 
of  uric  acid  in  the  blood  of  all  the  cases  of  diseases  of  the 
kidneys  that  he  examined,  and  his  results  were  confirmed 
by  Klemperer.  It  is  well  known  that  uratic  incrustation 
of  articular  cartilages  is  not  uncommonly  found  at  the 
post-mortem  examinations  of  subjects  who  have  never 
been    known    to   suffer   from    ostensible   gout   during   life. 

*  "  The    Uric   Acid    Diathesis,"    1894. 

t  Zeitschfift  f.   kUn.    Medicin,   xxiv.,   p.    512. 


Ch*p.  II.] 


RENAL    DISEASE    AND    GOUT. 


31 


Ord  and  Greenfield  *  examined  a  number  of  bodies  in 
the  post-mortem  room  for  the  existence  of  uratic  deposits 
in  the  joints,  and  the  presence  of  kidney  disease.  Among 
96  cases  presenting  lesions  of  the  kidneys,  uratic  deposits 
were  found  in  the  joints  of  18.  Norman  Moore, f  who 
bases  his  observations  on  the  results  of  a  large  number 
of  post-mortem  examinations,  states  that  chronic  inter- 
stitial nephritis  is  found  in  a  large  proportion  of  those 
bodies  in  which  sodium  urate  is  to  be  seen  in  the  joints. 
He  found  that  chronic  interstitial  nephritis  is  not  in- 
variably accompanied  by  the  presence  of  sodium  urate 
in  the  articular  cartilages,  though  it  is  usually  accom- 
panied by  traces  of  degeneration  in  some  of  the  articular 
cartilages.  He  examined  the  following  number  of  cases, 
all  of  which,  as  far  as  could  be  ascertained,  had  never 
suffered  from  ostensible  gout  : — 


Kidney  disease. 

No.  of  cases. 

Uratic  deposit  in 
joint  or  joints. 

Chronic  interstitial  nephritis  . 
Chronic  parenchymatous  nephritis 

53 
II 

25 
2 

Levison  J  is  a  strong  supporter  of  the  view  that  there 
is  always  some  degree  of  antecedent  renal  disease  con- 
nected with  gout.  In  reply  to  criticisms  of  this  view  he 
points  out  that  the  post-mortem  examinations  of  gouty 
patients  have  generally  shown  renal  lesions,  and  that  the 
few  exceptional  cases  are  open  to  criticism.  He  states 
that  all  the  post-mortem  examinations  of  patients  dying 
of  granular  kidney  disease  at  the  Communal  Hospital, 
Copenhagen,  during  a  period  of  fourteen  months,  showed 
uratic  deposits  in  one  or  other  of  the  joints,  although  most 


*  Trans,  of    the   International    Medical    Congress    at     London,  1881,  vol.  ii., 
p.  107. 

t  St.  Bartholomew's  Hosp.   Reports,   1887,  vol.  xxiii. 
X  Zeitschrift  /,  hiin-  Medicin,  1894,  xxvi.,  p.  293. 


32 


GOUT:    PATHOLOGY. 


[Part  1. 


of  the  patients    were    not   known   to  have  had    any  de- 
finite gouty  attack, 

I  thought  that  it  would  be  a  matter  of  interest  to 
ascertain  the  proportion  of  cases  of  uratic  deposition 
in  the  joints  occurring  in  subjects  in  whom  granular 
disease  of  the  kidneys  was  found  at  the  post-mortem 
examination,  and  in  connection  with  whom  the  pre- 
vious history  as  to  the  occurrence  or  not  of  gout  was 
known.  For  this  purpose  I  obtained  the  help  of  some 
of  the  pathologists  at  the  London  hospitals,  who  kindly 
examined  the  joints  in  such  cases  whenever  they  were 
able  to  do  so.  I  have  collected  altogether  the  results  of 
77  such  examinations,  for  which  I  am  indebted  to  the 
kindness  of  Cyril  Ogle,  F.  J.  Smith,  Hebb,  and  Jackson 
Clarke.  These  'j^  cases  were  all  cases  of  granular  kidney 
disease,  and  in  41  cases  uratic  deposits  were  found  in  one 
or  more  of  the  joints.  The  distribution  of  uratic  deposits 
among  the  gouty  and  non-gouty  cases  is  shown  in  the 
following  table  : — 

TABLE    II. 

Showiyig  the  results  of  the  examinations  of  the  joints  of  jy  cases  of 
granular  kidney  disease. 

Uratic  deposit  in 
joint  or  joints,   i 


Known  to  have  had  gout 
Never  known  to  have  had  gout 


Totals 


10 
31 


41 


In  the  10  cases  known  to  have  had  gout,  uratic  deposits 
were  found  in  one  or  more  of  the  joints  of  all,  and  the 
kidney  condition  was  in  every  case  described  as  "  markedly 
granular  "   or   "  fairly  granular." 

Among  the  67  cases  of  granular  kidney  disease  not 
known    to    have    suffered    from    previous    gouty    attacks, 


Chap.  II.] 


RENAL    DISEASE    AND    GOUT. 


33 


uratic  deposits  were  found  in  one  or  more  of  the  joints 
of  31 — that  is,  in  46  per  cent,  of  the  cases,  which  closely 
agrees  with  the  47  per  cent,  found  under  similar  conditions 
by  Norman  Moore.  In  these  67  cases  are  included  all 
cases  which  showed  the  existence  of  any  granular  kidney 
disease,  but  several  of  the  cases  in  which  no  uratic  deposits 
were  found  were  described  as  only  "  slightly  granular  " 
or  "  faintly  granular." 

If  from  the  67  cases  a  selection  is  made  of  those  described 
as  "  markedly  granular  "  or  as  "  typical  granular  kidneys," 
then  the  proportion  of  cases  in  which  uratic  deposits  were 
found   in   the   joints   appears   as   follows  : — 


No.  of  cases. 


Uratic  deposit  in 
joint  or  joints. 


Marked  granular  kidney  disease 


26 


Thus  it  is  seen  that  among  the  cases  of  marked  granular 
disease  of  the  kidneys  occurring  in  persons  who  were  never 
known  to  have  suffered  from  ostensible  gout  during  life, 
uratic  deposits  were  found  in  the  joints  of  ']']  per  cent. 
These  results,  taken  in  conjunction  with  those  of  Norman 
Moore  and  of  Levison,  show  that  kidney  disease  exercises 
a  powerful  influence  in  causing  an  accumulation  of  uric  acid 
in  the  blood,  and  consequently  in  producing  uratic  deposits 
in  the  joints. 

Gouty  afPeetions  of  the  kidneys  not  always  re- 
vealed clinically. — It  has  been  urged  that  if  kidney  dis- 
ease, with  the  consequent  diminished  excretion  of  uric 
acid,  be  the  primary  factor  in  the  causation  of  gout,  signs 
of  kidney  mischief  would  always  manifest  themselves 
prior  to  an  attack  of  gout,  and  that  very  few  such  cases 
«  have  ever  been  recorded.  But,  in  the  first  place,  it  must 
be  remembered  that  such  signs  are  not  usually  looked 
for,  and,  in  the  second  place,  they  need  not  necessarily 


34  GOUT:    PATHOLOGY.  [Part  i. 

reveal  themselves  clinically.  It  is  well  known  that  con- 
tracted granular  kidney  is  not  always  evidenced  either 
by  the  occurrence  of  albuminuria  or  of  dropsy.  The 
contention  that  if  organic  renal  failure  existed  the  urea 
excretion  would  probably  be  equally  affected  with  that 
of  uric  acid  does  not  hold  good,  if  the  view  is  adopted 
that  uric  acid  is  produced  in  the  kidneys,  while  urea 
is  only  eliminated  by  them.  It  is  well  known  that  in 
gouty  subjects  the  kidneys  have  been  found  at  the  post- 
mortem examination  in  a  diseased  condition,  when  there 
have  been  no  external  manifestations  during  life  of  the 
existence  of  such  renal  mischief.  That  uratic  deposits 
are  fq^uently  found  in  the  kidneys  of  gouty  subjects 
is  a  matter  of  common  experience,  but  in  the  absence 
of  such  deposits  the  kidneys  may  still  be  affected.  Sir 
Dyce  Duckworth  believes  that  changes  occur  in  the  kidneys 
of  gouty  subjects  quite  independently  of  uratic  deposits  in 
these  organs.  It  has  been  urged  that  the  renal  theory  is 
difficult  to  harmonise  with  the  hereditary  character  of 
gout.  It  is  quite  possible,  however,  that  there  may  be 
in  gouty  subjects  an  hereditary  tendency  to  the  renal 
affection,  since  both  Dickinson  and  Eichorst  have  shown 
that  there  is  an  hereditary  tendency  to  granular  kidney. 

Kidney  disease  and  gout  alike  caused  by  certain 
toxic  ag'ents. — Certain  toxic  agents  which  predispose 
to  or  which  excite  kidney  disease  are  also  known  to  pro- 
duce gout.  Lead  gives  rise  to  both  chronic  kidney  disease 
and  gout.  In  chronic  lead-poisoning  proliferation  of  the 
epithelium  of  the  urinary  tubules  first  occurs,  followed 
by  granular  atrophy  and  excessive  formation  of  inter- 
stitial tissue.  In  numerous  cases  of  chronic  lead-poisoning 
gout  has  developed.  Very  similar  changes  occur  in  the 
gouty  kidney,  and  to  the  advocates  of  the  renal  theory 
it  seems  reasonable  to  assume  that  the  changes  in  that 
organ  in  both  chronic  lead-poisoning  and  in  gout  so  affect 
the    excreting   apparatus    of   the    kidneys    as   seriously    to 


Chap.  II.]  ORIGIN    OF    URIC    ACID.  35 

diminish  their  power  of  ehminating  uric  acid.  That  lead- 
poisoning  gives  rise  to  the  accumulation  of  uric  acid  in 
the  blood  has  been  shown  by  Sir  Alfred  Garrod.  Gout 
subsequently  developed  in  two  cases  of  plumbism  in  which 
the  blood  was  found  by  him  to  be  rich  in  uric  acid.  He 
also  determined  the  excretion  of  uric  acid  in  the  urine  of 
two  patients  to  whom  acetate  of  lead  had  been  medicinally 
administered.  In  both  patients  a  well-marked  diminution 
of  uric  acid  in  the  urine  occurred.  It  was  also  noticed  that 
after  the  lead  had  been  given  for  a  day  or  two,  the  excretion 
of  the  uric  acid  in  the  urine  was  suddenly  diminished  to 
a  very  small  amount — a  condition  which  usually  lasted 
for  a  day  or  two.  This  points  to  the  fact  that  lead  exercises 
a  marked  inhibitory  effect  on  the  cells  of  the  kidneys  con- 
cerned in  the  excretion  of  uric  acid.  The  action  of  the 
lead  is  not  due  to  inhibition  of  the  formation  of  uric  acid, 
since  in  cases  of  plumbism  the  blood  becomes  charged  with 
uric  acid.  Alcohol  is  another  body  which  in  excessive 
quantities  gives  rise  to  kidney  mischief,  and  which  may 
also  give  rise  to  gout. 

View  that  the  liver  and  spleen  produce  uric  acid. 
■ — The  view  that  the  liver  was  the  seat  of  production  of 
uric  acid  probably  originated  in  the  knowledge  that  the 
excretion  of  uric  acid  in  the  urine  is  most  abundant  during 
digestion,  when  the  liver  is  most  active.  This  view  is, 
however,  equally  compatible  with  the  idea  that  the  liver 
merely  produces  the  antecedents  of  uric  acid.  The  in- 
vestigations of  Schroder  and  Minkowski  apparently  were 
strongly  in  favour  of  the  view  that  uric  acid  was  formed 
in  the  liver.  Schroder  *  states  that  the  liver  of  birds 
contains  a  high  percentage  of  uric  acid,  and  that  after 
removal  of  the  kidneys  uric  acid  continues  to  be  formed, 
and  accumulates  in  the  liver  and  blood.  The  last-mentioned 
statement  is  utterly  opposed  to  the  results  of  Zalesky's 
experiments  on  the  extirpation  of  the  kidneys  of  serpents. 

"■  "  Ludwig's  Festschrift,"  1887,  p.  89. 


36  GOUT:    PATHOLOGY.  [part  i. 

Minkowski  *  succeeded  in  keeping  geese  alive  from  six 
to  twenty  hours  after  extirpation  of  the  liver  ;  after  the 
operation,  their  urinary  excrement  contained  only  2  to 
3  per  cent,  of  uric  acid,  instead  of  the  normal  60  or  70 
per  cent.  This  diminished  excretion  of  uric  acid  after 
extirpation  of  the  liver  is,  however,  no  proof  that  the 
liver  is  the  seat  of  formation  of  uric  acid.  The  results 
are  equally  compatible  with  the  view  that  the  liver  is 
the  seat  of  production  of  the  antecedents  of  uric  acid 
only. 

Murchison  regarded  the  liver  as  the  seat  of  production 
of  uric  acid,  and  considered  that  the  presence  of  the  latter 
in  the  blood  or  tissues  was  due  to  functional  derangement 
of  the  liver,  in  consequence  of  which  the  metabolism  of 
some  of  the  albumen  became  arrested  at  the  stage  of  uric 
acid  formation,  instead  of  going  on  to  the  complete  stage 
of  urea  formation.  Charcot  regarded  the  liver  as  the 
principal  seat  of  production  of  uric  acid.  He  considered 
that  a  functional  derangement  of  the  liver  caused  the 
production  of  excessive  quantities  of  uric  acid,  and  its 
consequent  accumulation  in  the  blood.  Meissner  regards 
the  liver  of  fowls  in  the  normal  condition  as  the  principal 
source  of  uric  acid,  but  considers  that  the  spleen  and  the 
nervous  tissues  share  in  the  formation.  Ranke  was  of 
opinion  that  his  experiments  led  to  the  conclusion  that 
the  spleen  was  the  principal  organ  concerned  in  the  pro- 
duction of  uric  acid.  It  has,  however,  never  been  possible 
to  show  that  the  spleen  takes  any  active  part  in  developing 
gout.  On  the  contrary,  the  large  amount  of  uric  acid 
found  in  the  blood  of  cases  of  leukaemia  and  severe  anaemia 
shows  that  an  exaggerated  production  of  uric  acid  does 
not  by  itself  exert  any  influence  on  the  origin  of  gout. 

There  is  a  good  deal  of  experimental  evidence  to  show 
that  uric  acid  is  synthetically  formed  in  the  liver  of  birds, 
but  it  is  doubtful  whether  the  mammalian  liver  possesses 

*  Arch.  Exp,  Path.  w.  Pharmak.,  xxi. 


Chap,  ii]  THE    LIVER    AND    URIC    ACID.  37 

a  similar  power.  Indeed,  the  experiments  of  Sir  Lauder 
Brunton  on  the  hver  of  the  cat  tend  to  show  that  uric 
acid  can  be  destroyed  in  the  liver,  and  is  converted,  in 
part  at  least,  into  urea.  Rose  Bradford  *  contends  that 
in  the  case  of  birds,  notwithstanding  the  presence  of  urea 
in  the  blood,  the  evidence  would  seem  to  be  conclusive 
that  the  uric  acid  is  really  formed  by  the  liver.  Removal 
of  the  liver  in  birds  is  followed  by  the  diminution,  or  even 
the  disappearance,  of  uric  acid  from  the  urine,  and,  on 
the  other  hand,  the  ligature  of  tne  ureters  and — what  is, 
perhaps,  more  conclusive — destruction  of  the  kidney  cells 
by  the  injection  of  bichromate  of  potash  is  followed  by  the 
accumulation  of  uric  acid  in  the  blood,  and  even  by  its 
deposition  in  the  form  of  urates  in  various  organs  and 
cavities  of  the  body,  as,  for  instance,  the  liver  on  the  one 
hand  and  the  pericardium  on  the  other. 

The  disappearance  of  uric  acid  from  the  urine  after 
extirpation  of  the  liver  might,  of  course,  be  due  to  the 
urea  no  longer  being  formed  in  the  liver,  and  is  not  con- 
clusive evidence  of  the  formation  of  uric  acid  in  that  organ  ; 
but  Rose  Bradford  thinks  that  Ebstein's  results  showing 
the  accumulation  of  uric  acid  and  its  deposition  after 
destruction  of  the  renal  cells  with  bichromate  of  potash 
would  seem  to  negative  the  idea  that  this  substance  is 
formed  in  the  kidney.  In  his  opinion,  it  would  not  seem 
to  be  probable  that  a  function  which  is  discharged  by  the 
liver  in  one  set  of  vertebrates,  such  as  birds,  would  be 
discharged  by  another  organ,  as  the  kidney,  in  another 
set  of  vertebrates,  such  as  mammals,  and  therefore  it  is 
improbable  that  the  kidney  is  the  seat  of  the  formation 
of  uric  acid  in  mammals  and  in  man. 

Rose  Bradford,  therefore,  concludes  that  there  is  really 
but  little,  if  any,  evidence  in  favour  of  the  view  of  the 
kidney  having  a  special  secretory  activity,  although  per- 
haps it  would  be  unwise  to  deny  the  possibility  of  it. 

*  Lancet,  July  i6,  1904. 


38  GOUT:    PATHOLOGY.  [part  i. 

Views  that  uric  acid  is  produced  in  various 
tissues. — Ebstein,  who  attributes  in  cases  of  gout  the  main 
production  of  uric  acid  to  the  muscles  and  bone-marrow 
of  the  affected  extremities,  admits,  however,  that  the 
kidneys  may  take  a  part,  not  only  in  the  secretion,  but 
also  in  the  manufacture  of  uric  acid.  Robins  was  the 
first  to  formulate  the  view  that  uric  acid  is  formed  in 
connective  tissues  generally,  and  that  the  pathological 
condition  is  merely  an  exaggeration  of  the  physiological 
one.  This  view  therefore  regards  normal  fibrous  tissues 
as  the  seat  of  production  of  uric  acid,  and  considers  that 
in  gout  this  production  is  increased.  Chrzonsczewsky  also 
concludes  that  uric  acid  arises  in  connective  tissue,  and 
that  it  is  conducted  thence  through  the  lymphatic  vessels. 
Cantani  considers  that  the  connective  tissues  take  an 
active  part  in  the  formation  of  uric  acid,  and  that  in 
cases  of  gout  it  is  especially  produced  in  the  cartilages 
and  peri-articular  tissues  (ligaments,  tendons,  etc.).  Senator 
also  inclines  to  the  opinion  that  at  least  part  of  the  uric 
acid  is  formed  in  cartilaginous  tissue.  Most  writers  and 
observers  on  the  subject,  however,  consider  that  it  is  only 
certain  that  uric  acid  deposits  in  substances  of  the  con- 
nective-tissue class,  and  that  there  is  no  proof  that  uric 
acid  is  formed  in  connective  tissue. 

Views  that  excess  of  uric  acid  is  the  result  of 
an  animal  diet. — Another  commonly  received  notion  is 
that  gout  is  accompanied  by  an  excessive  formation  of 
uric  acid,  which  is  usually  attributed  to  the  ingestion 
of  a  too  highly  nitrogenised  diet,  and  especially  to  an 
animal  one.  Virchow,  however,  considers  that  a  too 
highly  nitrogenised  diet  is  not  necessarily  the  cause  of 
gout,  because  he  has  often  observed  gout  in  poorly-fed 
convicts.  Gout  is  certainly  not  incompatible  with  a 
vegetable  diet,  as,  amongst  certain  birds  kept  in  captivity 
and  living  exclusively  on  grain,  uratic  deposits  have  been 
observed  around  the  joints.     On  the  other  hand,  animal 


CHAP,  ii/i  DIET   AND    URIC    ACIU.  39 

food  does  not  necessarily  produce  uric  acid  in  a  healthy 
system,  as  is  shown  by  its  absence  from  the  urine  of  some 
of  the  carnivora.  It  has  for  a  long  time  been  held  that 
the  ingestion  of  very  large  quantities  of  proteid  matter 
is  followed  by  an  increased  production  of  uric  acid,  and 
vice  versa,  but  in  1899  Taylor  showed  that  the  amount 
of  ingested  proteid  has  absolutely  no  constant  relation 
to  the  quantity  of  uric  acid  excreted,  and  Jerome  con- 
cluded from  the  results  of  a  long  experiment  that  there 
is  at  present  no  proof  that  uric  acid  can  arise  in  man  in- 
dependently of  a  substance  containing  an  alloxur  or  purin 
group. 

That  the  production  of  uric  acid  is  not  dependent, 
at  all  events  to  any  great  extent,  on  diet  is  also  shown 
by  the  fact  that  the  same  diet  which  in  one  class  of  animals 
will  produce  uric  acid  will  in  another  class  produce  urea. 
Thus,  in  the  urine  of  the  carnivorous  lion  and  tiger  there 
is  a  quantity  of  urea  and  but  very  little  uric  acid  ;  on 
the  other  hand,  the  carnivorous  python  and  boa  excrete 
uric  acid  and  no  urea.  Graminivorous  birds  excrete 
uric  acid  and  no  urea,  whilst  herbivorous  mammals  ex- 
crete quantities  of  urea  and  but  little  or  no  uric  acid. 

Haig  claims  that,  in  addition  to  the  formation  of  uric 
acid  in  the  animal  economy,  the  gradual  introduction  of 
small  quantities  of  uric  acid  in  the  food  leads  to  its  gradual 
accumulation,  and  that  consequently  very  large  amounts 
may  be  stored  in  the  body  without  any  excessive  forma- 
tion having  taken  place.  Haig,  however,  does  not  produce 
any  proof  that  uric  acid  is  stored  up  in  the  system  apart 
from  gout.  The  contrary  is  proved  by  the  fact  that  in 
diseases  such  as  leukaemia,  severe  aneemia,  etc.,  although 
large  quantities  of  uric  acid  are  formed,  yet  they  are 
readily  eliminated  without  the  occurrence  of  storage  in  the 
system. 

Haig,  who  in  my  opinion  wrongly  ascribes  to  uric 
acid  an  almost  universal  role  in  the  causation  of  disease, 


40  GOUT:    PATHOLOGY.  [part  i, 

claims  that  the  uric  acid  excreted  in  the  urine  comes  from 
two  sources  : — (i)  The  uric  acid  which  is  formed  in  the 
body  out  of  nitrogenous  food ;  (2)  the  uric  acid  intro- 
duced into  the  body  ready-formed  in  certain  articles  of 
diet,  such  as  meat,  meat  extracts,  soup,  tea,  coffee,  etc. 
He  considers  that  flesh  diet  increases  both  the  introduction 
and  the  formation  of  uric  acid,  a  view  which  is  opposed 
to  the  previously  quoted  experimental  results  obtained 
by  Bleibtreu  and  by  Hirschfeld.  Haig  *  gives  the  quan- 
tities of  uric  acid  which  a  man  may  introduce  into  his 

system  with  an  ordinary  dinner  as  follows  : — 

grain. 
8  oz.  soup        .  .      containing  0.02  per  cent,  uric  acid   =   0.70 

2  oz.  fish  .  .  ,,  0.03         ,,  ,,  —   0.26 

3  oz.  meat  .  .  ,,  0.04  ,,  ,,  =  0.52 
J  drachm  meat  extract          ,,           0.80          ,,                  „          =0.24 

1.72 

As  far  as  I  can  ascertain  from  Haig's  writings,  he  has 
never  identified  by  the  murexide  test  this  uric  acid  reported 
to  be  present  in  these  various  articles  of  diet.  These 
estimations  depend  solely  on  the  application  of  Haycraft's 
process  to  the  articles  of  diet,  and  the  subsequent  calcula- 
tion of  the  silver  precipitate  so  obtained  in  terms  of  uric 
acid.  Recently  Haig  has  shown  a  tendency  to  shift  the 
responsibility  from  uric  acid  to  xanthin,  and  therefore 
refers  to  the  amounts  of  uric  acid  or  xanthin  which  he 
states  are  present  in  various  foods.  This  assumption,  that 
the  substance  stated  to  be  present  in  foods,  if  not  uric 
acid,  is  xanthin,  is  however  untenable,  since  xanthin  is 
not  estimated  by  Haycraft's  process. 

*  Brit,  Med.  Journ.,  1894. 


CHAPTER    III. 

PRIMARY   CAUSATION   OF   GOUT. 

The  uric  acid  compound  regarded  as  acting  passively  and  physic- 
ally— The  uric  acid  compound  regarded  as  acting  as  a  poison 
or  irritant — Uric  acid  not  a  poison --Necrotic  changes  as  the 
primary  cause  —  Inflammatory  or  degenerative  changes  as 
the  primary  cause  —  Nervous  disturbance  as  the  primary 
cause  —  Excess  of  carbonaceous  material  as  the  primary 
cause — A  bacterial  toxin  as  the  primary  cause  —The  liver  as 
a  toxin  destroyer. 

The  various  views  held  as  to  the  primary  cause  of  gout 
may  be  classified  into  the  following  groups  :  — 

1.  The  uric  acid  compound  regarded  as  acting  pas- 
sively and  physically  while  in  the  crystalline  state. 

2.  The  uric  acid  compound  regarded  as  acting  as  a 
poison  or  irritant  while  in  the  dissolved  state. 

3.  Necrotic  changes  in  the  affected  tissues  regarded  as 
the  primary  cause. 

4.  Inflammatory  or  degenerative  changes  in  the  affected 
tissues  regarded  as  the  primary  cause. 

5.  Nervous  disturbance  regarded  as  the  primary  cause. 

6.  Excess  of  carbonaceous  material  in  the  blood  re- 
garded as  the  primary  cause. 

7.  A  bacterial  toxin  regarded  as  the  primary  cause. 
These  various  views  will  now  be  considered  and  discussed. 

1.  The  uric  acid  compound  regrarded  as  acting" 
passively  and  physically  while  in  the  crystalline  state. 
— Sir  Alfred  Garrod  and  Sir  William  Roberts  have  been 
the  two  principal  exponents  of  this  view,  which  regards 
gout — in  so  far  as  its  phenomena  depend  on  uric  acid — . 

41 


42  GOUT:    PATHOLOGY.  [part  i. 

as  a  disease  the  manifestations  of  which  are  approximately 
due  to  mechanical  injury.  Sir  Alfred  Garrod  holds  that 
every  paroxysm  of  gout  is  attended  by  a  crystalline  deposit 
of  sodium  biurate,  and  that  this  deposit  exercises  chiefly 
a  mechanical  effect.  He  explains,  in  connection  with  arti- 
cular gout,  that  when  the  blood,  for  some  reason  or  other, 
is  incapable  of  holding  the  uric  acid  compound  in  solution, 
it  is  deposited  in  an  articular  cartilage  which  is  specially 
predisposed  for  its  reception.  Such  predisposition  is  gener- 
ally caused  by  its  being  the  seat  of  former  injury  or  disease. 
The  crystallisation  of  the  biurate  within  the  interstices 
of  the  cartilage  then  provokes  the  inflammatory  changes, 
so  that  the  deposition  is  the  cause  of  the  inflammation. 
Sir  William  Roberts  was  of  opinion  that  uric  acid  probably 
does  not  possess  any  inherent  poisonous  quality,  and 
that  as  long  as  it  remains  in  solution  it  produces  no  harm- 
ful results.  The  mischief  that  it  is  capable  of  producing 
only  results  from  its  precipitation  or  crystallisation  as 
sodium  biurate  in  the  tissues  or  fluids  of  the  body.  He 
considered  that  the  inflammation,  pain,  swelling,  and 
the  remoter  secondary  degenerative  changes  of  regular 
gout  are  quite  explicable  by  regarding  the  crystalline 
biurate,  which  is  precipitated  in  the  cartilaginous  and  fibrous 
structures  of  the  joints,  as  exerting  a  mechanical  action 
as  a  foreign  body.  Cornil  and  Ranvier  also  favour  the 
idea  that  the  crystalline  uratic  deposit  in  cartilages 
produces  inflammatory  changes  by  its  mechanical  irrita- 
tion. 

Sir  William  Roberts  even  held  that  the  manifestations 
of  irregular  gout  may  be  due,  like  the  arthritic  manifesta- 
tions, to  uratic  deposition' — that  is,  to  actual  precipitation 
of  crystals  of  sodium  biurate  into  the  connective  and  fibrous 
structures  of  the  implicated  organs,  whether  the  liver, 
heart,  lungs,  or  brain,  or  into  the  fibrous  sheaths  of  the 
nerves  controlling  the  functions  of  the  affected  viscera. 
He  was  further  of  opinion  that  the  presence  in  the  blood 


Chap.  Ill]  CAUSATION    OF   GOUT.  43 

of  scattered  needles  of  sodium  biurate  might  constitute 
foci  around  which  clotting  might  take  place,  and  that  the 
thromboses  not  unfrequently  observed  in  gouty  cases 
might  thus  be  accounted  for.  The  various  localities  in 
the  body,  apart  from  the  joints,  in  which  uratic  deposits 
have  been  found,  will  be  referred  to  later,  but  as 
regards  the  possible  deposition  of  sodium  biurate  in 
nervous  structures  constituting  the  exciting  cause  of  some 
of  the  pains  and  affections  of  different  viscera  peculiar 
to  irregular  gout,  it  may  be  of  interest  to  mention  here 
the  following  facts  :■ — Crystals  of  sodium  biurate  have 
been  found  by  Watson,  Gairdner,  and  Dafour  on  the 
cerebral  meninges  ;  by  Schroeder  van  der  Kolk  in  the 
neurilemma  of  peripheral  nerves  ;  and  by  Cornil  in  the 
cerebro-spinal  fluid. 

With  regard  to  the  manifestations  of  irregular  gout 
being  due  to  uratic  deposits  in  the  affected  viscera,  it  is 
true  that  observations  on  the  subject  are  very  limited 
in  number.  But,  in  the  first  place,  it  should  be  remem- 
bered that  such  irregular  uratic  deposits  are  extremely 
likely  to  escape  observation  in  the  post-mortem  room, 
unless  very  carefully  looked  for  with  the  aid  of  the  micro- 
scope ;  and,  in  the  second  place,  it  is  highly  probable 
that  such  deposits  would  become  dissolved  during  life 
as  the  attack  of  irregular  gout  passes  off. 

The  question  might  be  raised  that  if  the  crystalline 
biurate  always  acts  as  an  irritant,  why  should  not  the 
semi-solid  urinary  excrement  of  birds  and  serpents  set  up 
kidney  mischief  bv  acting  as  an  irritant  to  the  kidneys 
during  its  excretion  ?  The  reason  is  that  the  urinary 
excrement  of  birds  and  serpents  is  composed  of  an  amor- 
phous quadriurate,  and  that  in  the  amorphous  condition 
it  is  incapable  of  acting  as  an  irritant.  Moreover,  it  is 
possible,  as  Sir  William  Roberts  has  suggested,  that  the 
uratic  excrement  passes  through  the  tubules  of  the  kidneys 
of  birds  and  reptiles  in  the  gelatinous  form,  which  could 


44  GOUT:    PATHOLOGY.  [part  i. 

not  produce  the  mechanical  irritation  that  a  crystalUne 
deposit  would  be  liable  to  cause. 

To  the  view  that  a  sudden  deposition  of  crystals  of 
sodium  biurate  in  the  tissues  surrounding  the  joint  causes 
the  severe  pain  and  inflammatory  symptoms  of  acute 
gout,  it  has  been  objected  that  if  sodium  biurate  were 
an  irritant  and  the  inflammation  were  produced  by  its 
deposition  in  the  tissues,  then  that  inflammation  would 
not  subside  as  long  as  the  irritant  remained.  If  an  irritant 
foreign  body  remains  in  an  organ,  it  is  impossible  that  the 
inflammation  caused  by  that  irritant  should  subside  while 
the  irritant  actually  increases,  for  after  each  attack,  and 
in  the  intervals  between  the  attacks,  the  deposits  of  sodium 
biurate  enlarge.  Therefore  the  fact  that  the  inflammation 
of  the  joint  or  tissue  in  which  sodium  biurate  is  deposited 
subsides  while  the  deposition  remains  and  increases  serves 
to  negative  the  theory  that  such  deposition  is  the  cause 
of  the  inflammation.  It  is  much  more  probable  that 
inflammation  precedes  deposition  of  biurate,  and  that  the 
deposition  of  sodium  biurate,  which  takes  place  in  the  tissues 
of  and  around  a  joint  after  an  attack  of  gout,  is  subsequent 
to  the  attack.  During  an  attack  the  joint  is  distended 
with  synovial  fluid  rich  in  sodium  quadriurate  or  biurate  ; 
the  spaces  in  the  periarticular  areolar  tissue  are  also  dis- 
tended with  blood-serum  containing  one  or  both  of  the 
uric  acid  salts.  As  the  attack  subsides  and  the  local 
temperature  falls,  crystallisation  of  sodium  biurate  occurs 
in  the  effused  fluid,  brought  about  in  part  by  the  fall  of 
temperature,  in  part  by  the  conversion  of  the  more  soluble 
quadriurate  into  the  less  soluble  biurate,  and  in  part  by 
the  absorption  of  the  more  watery  part  of  the  effused 
fluid. 

2.  The  uric  acid  compound  regrarded  as  acting"  as 
a  poison  op  irritant  while  in  the  dissolved  state.— 
This  view,  while  holding  that  the  uric  acid  compound  is 
the  primary  cause  of  gout,  regards  it  as  producing  morbid 


CHAP.  III.]  URIC    ACID    NOT   TOXIC.  45 

changes  in  the  structure  of  tissues  while  remaining  in  the 
dissolved  state.  Many  writers  and  observers  have  sup- 
ported the  view  that,  apart  from  the  local  trouble  in  the 
joints  caused  by  the  deposited  sodium  biurate  acting  as 
an  irritant,  the  soluble  uric  acid  compound  which  is  cir- 
culating in  the  fluids  of  the  body  acts  as  a  poison,  the 
toxic  effects  of  which  are  responsible  for  a  number  of  the 
symptoms  associated  with  the  gouty  state.  Pfeiffer  holds 
the  somewhat  peculiar  view  that  a  compound  of  uric  acid 
is  deposited  in  both  healthy  and  diseased  portions  of  the 
body — apparently  without  producing  any  marked  symp- 
toms'— and  that  an  acute  attack  of  gout  is  caused  by  the 
blood  re-dissolving  this  deposited  uric  acid  compound, 
-owing  to  a  temporary  increase  in  the  alkalinity  of  the 
blood,  and  that  dissolved  in  the  blood  in  this  concentrated 
form  the  uric  acid  compound  acts  as  a  chemical  poison. 
That  this  view  is  untenable  is  evident  when  it  is  remem- 
bered that  uric  acid  is  deposited  as  the  sodium  biurate, 
and,  as  will  be  shown  later,  the  solubility  of  this  body  in 
a  fluid  medium  is  not  heightened  by  an  increased  alkalinity 
of  that  medium. 

Uric  acid  not  a  poison. — Sir  William  Roberts*  argues 
that  the  acceptance  of  the  theory  that  uric  acid  possesses 
a  toxic  action  is  difficult  for  the  following  two  reasons  :• — 
(i)  That  there  is  no  direct  experimental  proof  that  uric 
acid  is  a  toxic  agent  ;  and  (2)  that  although  the  fluids  of 
the  body  of  a  gouty  man,  on  the  eve  of  an  outbreak  of 
acute  gout,  are  impregnated  with  sodium  biurate  to  satura- 
tion, yet  such  a  person  does  not  show  any  signs  of  poison- 
ing, but  enjoys  complete  immunity  from  toxic  symptoms 
until  the  sudden  advent  of  the  arthritic  attack.  Another 
fact  which  is  strongly  opposed  to  the  view  that  uric  acid  is 
a  toxic  agent  is  that  in  cases  of  leukaemia  and  severe 
anaemia  the  blood  is  frequently  highly  charged  with  uric 
acid  in  the  form  of  sodium  quadriurate  without  the  pro- 

*  Croonian  Lectures  :    "  Uric  Acid  Gravel  and  Gout,"   1892. 


46  GOUT:    PATHOLOGY.  [part  l 

duction  of  any  toxic  symptoms  that  could  be  referred  to 
the  uric  acid  compound. 

When  Sir  Alfred  Garrod  discovered  that  uric  acid  was 
present  in  the  blood  of  patients  during  an  attack  of  gout 
it  was  naturally  supposed  that  the  symptoms  of  gout  were 
due  to  the  presence  of  this  body  in  the  blood  and  tissues. 
If  uric  acid  is  the  cause  of  gout,  it  must  be  shown  that 
uric  acid  will  produce  toxic  effects  or  produce  some  of  the 
symptoms  of  gout.     This,  however,  has  never  been  done. 

In  support  of  the  belief  that  uric  acid  is  practically 
devoid  of  toxic  properties,  the  following  facts  may  be  put 
forward  : — (i)  Animals  have  been  made  to  ingest  large 
quantities  of  uric  acid  with  their  food,  and  urates  in  solu- 
tion have  been  freely  injected  into  their  veins,  without 
eliciting  any  signs  of  poisoning  ;  (2)  experiments  on  frogs' 
muscles  have  shown  that  muscle  rigidity  and  tetanus  are 
produced  by  hypoxanthin,  but  that  uric  acid  is  inert  ; 
(3)  after  carefully  searching  the  literature  on  the  subject, 
the  only  evidence  I  can  find  of  discomfort  following  the 
ingestion  of  uric  acid  is  the  statement  of  Walker  Hall, 
who,  after  taking  large  doses  of  uric  acid,  had  malaise 
and  headache  lasting  for  several  hours  :  almost  any  sub- 
stance, however  (common  salt,  for  example),  will  produce 
toxic  effects  if  taken  in  very  excessive  quantities  ;  (4)  in 
leukaemia  the  blood  contains,  for  a  long  time,  a  large  quan- 
tity of  uric  acid,  more  than  double  the  amount  present  in 
most  cases  of  gout,  yet  there  are  no  symptoms  whatever 
in  common  between  the  two  diseases,  and  no  symptoms 
that  could  be  referred  to  uric  acid  are  ever  present  in  this 
disease — this  in  itself  shows  that  uric  acid  can  have  no 
toxic  effect  ;  (5)  Ransom,  of  New  York,  has  demonstrated 
the  non-toxic  properties  of  uric  acid  by  the  following  ex- 
periments. In  two  cases  of  chronic  nephritis  three  grammes 
of  uric  acid  were  given  by  the  mouth  in  twenty-four  hours 
for  three  days  in  succession.  A  decided  increase  was 
found  in  the  urine  during  the  time,  but  there  was  no  sys- 


Chap.  Ill]  URIC    ACID    NOT   TOXIC.  47 

temic  disturbance.  In  one  case  of  chronic  nephritis,  three 
grammes  were  given  in  twenty-four  hours  for  three  days 
in  succession,  and  on  the  fourth  day  six  grammes  were 
given,  without  producing  any  systemic  disturbance.  In 
four  cases  of  clironic  gout,  a  diet  of  shad  roe  was  given  for 
five  days,  which  caused  a  decided  increase  in  the  excretion 
of  uric  acid  in  the  urine,  but  no  disturbance  of  the  health. 
In  two  rabbits,  two  successive  intravenous  injections  of  one 
gramme  each  of  uric  acid  were  made  without  systemic  dis- 
turbance, though  a  large  part  of  the  acid  was  recovered 
from  the  urine.  In  two  dogs,  two  successive  intravenous 
injections  of  two  grammes  each  of  uric  acid  were  not  fol- 
lowed by  any  disturbance,  while  the  urine  showed  a  large 
increase. 

Not  only  in  the  medical  world  has  an  unmerited  im- 
portance been  attached  to  uric  acid  as  a  factor  in  the  causa- 
tion of  disease,  but  unfortunately,  among  a  considerable 
section  of  the  public  there  has  arisen  a  fetichism  of  uric 
acid,  which  has  been  pandered  to  and  fostered  by  the  pro- 
prietors of  the  various  quack  remedies  that  are  so  persis- 
tently advertised  as  being  capable  of  dissolving  or  re- 
moving uric  acid  from  the  system.  The  time  has  come 
clearly  to  recognise  that  uric  acid  possesses  no  toxic  pro- 
perties worth  speaking  of.  The  joint  manifestations  of 
gout  are  dependent  upon  much  more  general  and  much 
larger  conditions  than  a  mere  excess  of  uric  acid  in  the 
blood.  The  deposition  of  sodium  biurate  is  merely  the 
sign  of  the  disease,  not  the  essence  of  it.  In  fact,  the  role 
of  uric  acid  in  gout  may  well  be  compared  with  that  of 
sugar  in  diabetes.  Ringrose  Gore  has  well  pointed  out 
that  uric  acid  can  be  no  exception  to  the  general  law  that 
a  substance  acts  as  a  poison  in  direct  proportion  to  the 
amount  of  it  present  in  the  circulating  fluids. 

Alloxur  bases  regarded  as  the  -poison  of  gout. — 
Kolisch  *    considers    that    some    antecedents    or    allies    of 

*   Wien.  klin.   Woch.,  1895. 


48  GOUT:    PATHOLOGY. 


[Part  I, 


uric  acid  are  responsible  for  the  toxic  effect  which  he 
beheves  constitutes  the  primary  cause  of  gout.  His  view 
is  that  the  graver  manifestations  of  gout  only  make  their 
appearance  when  the  functions  of  the  kidneys  become 
impaired  from  any  cause,  and  since  he  finds  that  in  the 
urine  of  the  gouty  there  is  an  increase  of  alloxuric  substances, 
and  also  that  alloxur  bases  cause  changes  in  the  kidneys 
resembling  parenchymatous  degeneration,-  he  infers  that 
these  bases  are  concerned  in  the  production  of  the  kidney 
affection  which  precedes  the  development  of  gout.  His 
theory  is  that  during  normal  action  of  the  kidneys  the 
greater  part  of  the  alloxur  bases  is  excreted  as  uric  acid  ; 
but  when  the  structures  which  form  uric  acid  are  enfeebled 
there  is  an  increased  excretion  of  alloxur  bases,  with  cour 
comitant  toxic  effects.  Kolisch's  views  have  received  some 
confirmation  by  Weintrand,*  who  has  also  found  an  ex- 
cessive excretion  of  alloxuric  substances  in  the  urine  of 
gouty  patients.  On  the  other  hand,  they  are  controverted 
by  the  observations  of  Schmoll,-)*  His,:j;  Laquer,§  and 
Mafatti,!|  who  failed  to  find  any  increased  excretion  of 
alloxuric  substances  in  the  urines  of  gouty  patients. 

3.  Necrotic  changes  in  the  affected  tissues  regarded  as 
the  ppimary  cause  of  gout,  the  necrosis  being  due  to 
the  presence  of  dissolved  urates. — Ebstein,^  who  has  de- 
voted a  considerable  amount  of  time  to  the  experimental 
study  of  the  causation  of  gout,  is  the  great  exponent  of 
this  view.  His  theory  is  that  a  destructive  or,  as  he  terms 
it,  a  necrotising  process  is  produced  in  the  cartilages  or 
other  implicated  tissues  by  uric  acid  in  one  form  of  com- 
bination, and  that,  following  this,  the  uric  acid  in  another 
form  of  combination  is  deposited  in  the  necrosed  areas. 
In  other  words,  that  a  destructive  process  always  precedes 

*  Charite  Annalen,  1895,  xx. 

t  Zeitschrift  f.   klin.    Medicin,    1896,   xxix. 

j  Berlin,    klin.    Woch.,    1896,    xxxiii. 

§   Verhandlitngen  des  Cong.  f.   innere  Med.,   1896,   xiv. 

II   Wien.  klin.    Woch.,   1896,  ix. 

^  "  Die  Natur  und  Behandlung  der  Gicht,"  1882. 


CHAP.  Ill]  EBSTEIN'S    EXPERIMENTS.  49 

the  process  of  deposition,  both  processes  being  due  to  uric 
acid,  but  in  different  states  of  combination.  Ebstein 
maintains  that  uratic  crystals  only  form  in  necrotic  tissues, 
never  in  healthy  tissues.  He  regards  the  necrosis  of  tissue 
and  the  subsequent  uratic  deposits  as  together  constitut- 
ing the  characteristic  ensemble  of  the  gouty  process.  His 
theory  assumes  that  the  irritant  is  the  neutral  sodium 
urate  in  the  dissolved  state,  and  that  the  first  step  in  the 
gouty  process  consists  in  a  stasis  of  the  lymph  stream,  fol- 
lowed by  the  infiltration  of  the  tissue  in  circumscribed 
areas  by  the  lymph  containing  the  dissolved  neutral  urate. 
The  neutral  urate,  according  to  his  view,  acts  as  a  chemical 
irritant,  and  sets  up  a  necrotising  process  in  the  implicated 
tissues,  and  finally  produces  complete  necrosis  of  the  tissues 
in  the  affected  areas.  The  necrotising  and  necrotic  por- 
tions of  the  tissues  provoke  irritation  of  the  surrounding 
parts,  and  so  produce  the  inflammatory  phenomena  of  gout. 
Ebstein  assumes  that  the  process  of  necrosis  generates  a 
free  acid,  which  converts  the  neutral  urate  present  in  the 
fluids  of  the  body  into  the  acid  urate,  which  substance  is 
then  deposited  in  the  crystalline  form  in  the  fully  necrosed 
areas.  No  mention  is  made  of  the  nature  or  name  of  this 
hypothetical  acid. 

Ebstein's  experiments. — To  support  this  theory  Ebstein 
relies  upon  two  different  classes  of  experiments  conducted 
by  him.  One  class  consists  of  his  examination  of  the 
organs  and  tissues  of  birds  that  he  considered  he  had  ren- 
dered gouty,  by  preventing  the  elimination  of  their  urinary 
secretion.  The  other  class  of  experiment  consists  of  ob- 
servations on  the  irritant  effect  of  a  solution  of  a  sodium 
urate  on  the  delicate  corneal  tissue  of  the  eye.  As  I  ven- 
ture to  differ  from  the  deductions  that  Ebstein  has  drawn 
from  his  experiments  and  observations,  I  propose  to  de- 
scribe his  methods  of  experimentation,  and  briefly  to  criti- 
cise his  deductions  therefrom. 

Ehstein's    experiments    on    birds: — Ebstein's  first   series 


50  GOUT:    PATHOLOGY.  [part  i, 

of  experiments  consisted  in  an  endeavour  to  induce  in 
cocks  a  condition  which,  from  the  anatomical  point  of 
view,  he  considered  was  analogous  to  the  gouty  state  in 
man.  This  he  effected  by  preventing  the  elimination  of 
their  urinary  uratic  secretion  in  two  ways — {a)  by  ligatur- 
ing the  two  ureters,  and  so  damming  back  upon  the  circula- 
tion the  urates  which  would  otherwise  have  passed  away  ; 
and  (b)  by  administering  to  the  cocks  small  and  repeated 
subcutaneous  injections  of  the  neutral  potassium  chromate, 
which  Ebstein  considers  inhibits  the  passage  of  uric  acid 
through  the  kidneys  by  its  action  on  the  renal  parenchyma, 
and  so  causes  a  damming  back  upon  the  circulation  of  a 
portion  of  the  urates,  which  normally  are  excreted  in  their 
entirety  by  the  kidneys.  In  the  bodies  of  the  birds  experi- 
mented on  uratic  deposits  were  found  in  the  articulations, 
in  the  tendon-sheaths,  in  the  liver,  and  in  the  muscular 
tissues.  Ebstein  found  that  the  deposition  of  urates  was 
much  more  copious  and  more  widely  spread  in  the  cocks 
experimented  on  by  injection  of  potassium  chromate  than 
in  those  whose  ureters  were  ligatured.  This  difference 
he  referred  to  the  fact  that  he  could  keep  the  birds  alive 
for  a  long  time  while  subjecting  them  to  the  action  of  potas- 
sium chromate,  whereas  after  ligaturing  both  ureters  they, 
as  a  rule,  only  lived  for  about  twenty-four  hours.  As  the 
result  of  these  experiments  Ebstein  came  to  the  following 
conclusions  : — (i)  That  necrosing  and  necrotic  processes 
are  developed  in  various  organs  as  the  result  of  some  irri- 
tant ;  (2)  that  uratic  deposits  form  in  the  necrotic  areas 
which  in  appearance  resemble  the  gouty  deposits  of  man  ; 
(3)  that  a  reactive  inflammation,  with  infiltration  of  small 
cells,  is  set  up  in  the  neighbourhood  of  these  necrotic  areas. 
Criticism  of  Ehstein's  experiments  on  birds: — This 
class  of  experiments  consisted  of  observations  of  the 
uratic  deposits  formed  in  fowls  when  the  elimination 
of  their  uric  acid  is  prevented  either  by  ligaturing  the 
i^reters,  or  by  the  progressive  disablement  of  the  kidneys 


CAP.  III.]  EBSTEIN'S    EXPERIMENTS.  51 

by  repeated  subcutaneous  injections  of  potassium  chromate. 
I  do  not  think  that  the  morbid  processes  occurring  under 
these  conditions  in  fowls  can  be  considered  as,  in  any  sense, 
comparable  with  those  occurring  in  connection  with  gout 
in  man.  Ebstein  found  uratic  deposits  in  the  liver  and 
muscular  tissues  of  the  birds  experimented  on,  localities 
where  they  are  not  found,  at  all  events  to  any  appreciable 
extent,  in  human  gout.  From  this  one  may  fairly  conclude 
that  the  two  processes  cannot  be  considered  as  comparable. 
Moreover,  since  the  fowl  produces  and  eliminates  by  the 
kidneys  so  large  a  quantity  of  urates,  the  more  or  less  sudden 
stoppage  of  kidney  excretion  must  necessarily  result  in 
the  damming  back  of  it  and  the  rapid  accumulation  of  it 
in  the  blood  and  tissues,  where,  as  Sir  William  Roberts 
suggests,*  it  would  probably  first  collect  in  a  state  of  solu- 
tion as  the  quadriurate,  which  would  then  be  precipitated 
in  the  tissues  as  the  gelatinous  biurate,  and  this  in  its  turn 
would  be  changed  into  the  crystalline  biurate. 

EhsteifCs  experiments  with  urates. — It  is  on  the  second 
class  of  experiments  that  Ebstein  depends  for  proof  of  his 
assumption  that  the  neutral  sodium  urate  is  capable  of 
acting  as  a  chemical  irritant  to  the  tissues,  and  of  produc- 
ing in  them  the  necrotising  changes  which  subsequently 
lead  to  complete  necrosis  of  the  affected  areas  of  the  im- 
plicated tissues.  In  order  to  show  that  a  combination  of 
uric  acid  with  sodium  acted  as  an  irritant,  Ebstein  took  a 
saturated  solution,  prepared  at  100°  F.,  of  uric  acid  in  a 
5  per  cent,  solution  of  sodium  phosphate,  and  injected  it 
into  the  peritoneal  cavity,,  into  the  kidney,  into  the  anterior 
chamber  of  the  eye,  into  the  cartilage  of  the  ear,  and  into 
the  cornea  of  a  rabbit.  Powdered  uric  acid  was  also  intro- 
duced by  insufflation  into  the  conjunctival  fold  of  one  eye. 
Very  appreciable  changes  were  produced  in  the  cornea 
only,  and  it  was  in  this  structure  that  Ebstein  studied  what 
he  considers  were  the  irritant  or  toxic  effects  of  uric  acid. 

*  Croonian   Lectures  :     "  Uric  Acid  Gravel  and    Gout,"    1892. 


52  GOUT:    PATHOLOGY.  [paht  i. 

He  found  that  these  injections  produced  a  modified  form 
of  inflammation  in  the  tissues  of  the  cornea.  As  a  control 
experiment  he  injected  into  the  cornea  of  the  other  eye  a 
simple  solution  of  sodium  phosphate,  or  water  containing 
calcined  magnesia  in  suspension,  neither  of  which  pro- 
duced any  inflammatory  changes.  He  therefore  inferred 
that  the  inflammatory  changes  were  set  up  in  the  cornea 
by  the  urate  in  solution  acting  as  a  chemical  irritant. 

Criticism  of  Ebstein's  experiments  with  urates.- — The 
objection  to  this  method  of  experimentation  is  that,  in  the 
first  place,  the  solution  of  uric  acid  in  sodium  phosphate 
does  not  contain  the  neutral  sodium  urate,  which  is  the 
body  on  which  Ebstein  relies  for  the  production  of  the 
initial  irritant  effects  leading  on  to  the  necrotising  process. 
The  solution  would  contain  the  sodium  quadriurate  or  the 
biurate,  or  a  mixture  of  the  two.  Moreover,  as  Sir  William 
Roberts  has  pointed  out,  such  a  saturated  solution  would 
soon  begin  to  deposit  its  urate  in  the  form  of  the  gelatinous 
biurate,  which,  infiltrating  the  affected  area  of  the  corneal 
tissue,  would  act  as  a  mechanical  irritant.  It  is,  therefore, 
clear  that  all  the  corneal  changes  observed  by  Ebstein 
can  be  accounted  for  by  the  assumption  that  they  are 
caused  by  a  mechanical  irritant.  The  experiments  of 
Neubauer  are  opposed  to  the  view  that  a  soluble  urate 
circulating  in  the  blood  can  act  as  a  poison  or  irritant  and 
start  necrosis.  He  found  that  the  administration  of  large 
quantities  of  uric  acid  to  rabbits  (as  much  as  twelve  grammes 
in  some  cases)  did  not  seem  to  cause  any  inconvenience. 
Moreover,  is  it  likely  that  solutions  of  urates  should  act  as 
irritants,  when  their  passage  through  the  kidneys  is  part 
of  the  natural  elimination  of  nitrogen  in  man  ?  If  solutions 
of  the  urates  are  to  be  regarded  as  irritants,  then  the  kid- 
neys would  never  escape  damage. 

Another  important  argument  which  militates  against 
the  acceptance  of  Ebstein's  theory  is  that  not  only  is  there 
no  proof  that  the  neutral  sodium  urate,  upon  which  he 


Chap.  Ill]  EBSTEIN'S    EXPERIMENTS.  53 

depends  for  the  starting  of  the  gouty  changes,  ever  exists 
in  the  human  body,  but,  on  the  other  hand,  there  is  strong 
evidence  to  show  that  it  never  can  exist  in  the  human  body. 
The  neutral  sodium  urate  is  an  extremely  caustic  and  un- 
stable compound,  and  is  decomposed  in  the  presence  of 
carbonates,  so  that  it  is  impossible  for  it  to  exist  in  the 
blood.  The  first  factor  upon  which  Ebstein  relies  for  his 
theory  of  the  causation  of  gout  therefore  disappears.  More- 
over, the  responsibility  for  the  assumed  necrotic  changes 
cannot  be  transferred  from  the  neutral  sodium  urate  to 
the  biurate,  since  Pfeiffer  has  shown,  by  means  of  subcutane- 
ous injections  of  a  solution  of  a  biurate,  that  although  it  can 
produce  pain  and  irritation,  yet  it  cannot  cause  necrosis, 
especially  when  in  so  weak  a  solution  as  must  occur  in  the 
human  body.  The  assumption  by  Ebstein  that  the  process 
of  necrosis  generates  an  acid  which  is  supposed  by  him  to 
convert  the  neutral  urate  into  the  acid  urate  is  based  on  an 
imperfect  acquaintance  with  the  chemistry  of  the  urates. 
Sir  William  Roberts  has  shown  that  uric  acid  is  primarily 
taken  up  by  the  blood  and  lymph  as  a  quadriurate- — not  as 
a  neutral  urate — and  he  has  also  proved  that  the  foiTuation 
and  deposition  of  the  crystalline  biurate  are  not  favoured 
by  the  intervention  of  an  acid.  Moreover,  in  connection 
with  leukaemia,  severe  anaemia,  and  other  diseases,  to  which 
reference  will  be  made  later,  we  know  that  a  considerable 
quantity  of  uric  acid  may  be  present  in  the  blood  in  the 
form  of  sodium  quadriurate  without  giving  rise  to  necrosis 
of  tissues  anywhere. 

4.  Inflammatory  or  deg^enerative  changes  in  the 
affected  tissues  reg-arded  as  the  primary  cause  of  g^out, 
such  initial  changes  not  being  caused  by  urates.— Ord  in 
1872  considered  that  gout  was  due  to  a  special  form  of  de- 
generation in  some  of  the  fibroid  tissues,  resulting  in  an  ex- 
cessive formation  of  sodium  urate,  which  is  then  discharged 
into  the  blood,  and  is  subsequently  deposited  in  those  parts 
least  freely  supplied  with  vascular  and  lymphatic  structures. 


54  GOUT:    PATHOLOGY.  [part  i. 

Ord,  whose  views,  in  this  particular,  have  been  sup- 
ported by  Norman  Moore  and  Bowlby,  also  considers 
that  uratic  deposits  only  occur  in  tissues  which  have  pre- 
viously begun  to  degenerate. 

Berkart  *  considers  that  the  severity  of  the  local  symp- 
toms attending  an  attack  of  acute  gout  is  inconsistent 
with  the  assumption  that  they  are  produced  by  a  primary 
chondritis,  due  to  irritation  set  up  by  the  deposition  of 
sodium  biurate  in  the  articular  cartilages.  He  considers 
that  the  role  of  the  uric  acid  is  one  of  a  humbler  kind  than 
that  which  has  hitherto  been  attributed  to  it.  In  his 
opinion  the  uratic  deposits  are  most  frequently  connected 
with  a  form  of  panarthritis,  or  a  general  inflammatory 
affection  of  the  joints,  which  chiefly  affects  the  smaller 
joints  of  the  extremities.  Without  assuming  any  identity 
between  arthritis  deformans  and  gout,  he  considers  that 
in  both  instances  the  disease  probably  originates  in  some 
kind  of  atrophy  of  the  substance  of  the  bone,  that  the 
degenerative  process  then  attacks  the  cartilages  and  fibrous 
tissues  of  the  joints,  and  that  following  on  this  there  occurs 
a  necrosis j)f  the  tissues  close  to  or  within  the  joint.  This 
necrosis,  he  considers,  is  the  primary  cause  of  the  pain, 
hypersemia,  collateral  oedema,  and  desquamation  of  the 
skin  of  the  affected  joint.  The  degeneration  and  necrosis 
of  the  tissues  are  the  result  of  a  profound  disturbance  of 
nutrition.  Berkart  attributes  the  presence  of  the  urates 
in  the  blood  in  part  to  leucocytosis,  and  in  part  to  the  for- 
mation of  uric  acid  from  the  disintegration  of  the  tissues  ; 
so  that  he  regards  the  uratic  deposits  as  an  epiphenomenon, 
and  not  as  the  cause  of  the  gouty  paroxysm. 

George  W.  Balfour  f  holds  that  an  acute  attack  of  gout 
is  not  truly  inflammatory,  but  results  from  thrombosis  of 
small  vessels  around  the  affected  joint.  According  to  his 
view,  the  occurrence  of  such  thrombosis  accounts  for  the 

*  Brit.  Med.  Journ.,  1895,  vol.  i. 
t  Edinburgh  Med.  Journ.,  1898,  iii. 


Chap.  III.]  NERVOUS    DISTURBANCE.  55 

sudden  onset  of  acute  pain  in  the  affected  joint.  The 
events  which  follow  are  due  to  the  formation  of  an  aucemic 
area  in  and  around  the  joint,  viz.,  early  visible  turgidity  of 
the  veins  leading  from  the  affected  part,  followed  by  swell- 
ing due  to  accumulation  of  plasma  within  the  ansemic 
area,  and,  lastly,  tension  of  the  skin.  He  considers  that 
the  deposition  of  sodium  biurate  is  simply  due  to  the 
accumulation  of  blood  plasma  containing  it  in  solution 
within  the  ansemic  area  of  the  joint,  and  that  the  deposit 
is  neither  the  result  nor  the  cause  of  any  inflammatory 
action. 

5.  Nervous  disturbance  regrarded  as  the  primary  cause 
of  grout.' — The  view  that  gout  is  intimately  connected  with 
disturbances  of  the  nervous  system  has  many  supporters. 
Cullen,  the  great  opponent  of  the  humoral  theory  in  the 
latter  half  of  the  last  century,  considered  that  gout  mainly 
depended  on  an  affection,  of  the  nervous  centres.  Sir 
Dyce  Duckworth,*  while  accepting  the  view,  as  previously 
mentioned,  that  uric  acid  has  some  connection  with  gout, 
considers  that  gout  is  primarily  dependent  on  a  functional 
disorder  of  a  definite  tract  of  the  nervous  system,  and  that 
the  part  specially  involved  is  possibly  situated  in  the 
medulla  oblongata,  where  it  may  be  that  there  is  a  trophic 
centre  for  the  joints.  One  reason  that  Sir  Dyce  Duck- 
worth gives  for  considering  this  possible  is  the  relationship 
of  gout  to  diabetes,  the  consideration  of  which  has  led  him 
to  the  behef  that  the  portions  of  the  nervous  system  in- 
volved in  the  two  diseases  cannot  be  far  apart  from  one 
another.  In  consequence  of  this  disorder  of  the  neuro- 
trophic system  defects  of  nutrition  arise  which  not  only 
cause  undue  formation  of  uric  acid,  but  also  inhibit  the 
normal  destruction  of  that  body  in  the  tissues  ;  at  the  same 
time  the  renal  excretory  power  for  uric  acid  appears  to  be 
temporarily  inhibited  as  part  of  the  process  of  the  gouty 
paroxysm, 

*  "  A  Treatise  on  Gout,"   1889.    -  ■  '  . .,  , 


56  GOUT:    PATH(3L0GY.  [part  i. 

Sir  Dyce  Duckworth,  therefore,  regards  gout  as  belong- 
ing to  the  class  of  neuro-humoral  diseases,  but  he  does  not 
at  present  insist  on  the  localisation  of  the  primary  disturb- 
ance in  a  limited  portion  of  the  cerebro-spinal  axis.  He 
draws  the  following  distinction  between  inherited  and 
acquired  gout.  In  primary  or  inherited  gout  the  toxaemia 
is  dependent  on  the  inherited  gouty  neurosis.  In  second- 
ary or  acquired  gout  the  toxaemia  arises  from  the  digestive 
and  excretory  organs  becoming  overloaded,  and  then,  if 
with  this  toxaemia  there  is  depression  and  exhaustion  of 
the  nervous  system,  the  gouty  neurosis  may  be  established 
by  the  morbid  blood  condition  affecting  the  nutrition  of  the 
nervous  system.  Sir  Dyce  Duckworth  claims  that  the 
suddenness  with  which  an  acute  attack  of  gout  comes  on, 
preceded  as  it  is  usually  by  a  sense  of  well-being  in  the 
patient,  is  indicative  of  the  nervous  origin  of  the  out- 
break, and  that  it  is  to  the  instability  and  undue  sensitive- 
ness of  the  nervous  system  in  the  gouty  that  the  manifesta- 
tions of  the  paroxysm  are  due. 

Edward  Liveing  *  considers  that  there  is  much  to  be 
said  in  support  of  the  view  that  gout  is  the  manifestation  of 
a  disorder  which  has  its  primary  seat  in  the  nervous  system. 
He  remarks  that  the  view  that  uric  acid  exerts  a  toxic 
influence  upon  the  nervous  centres,  and  that  the  particular 
character  of  the  disorder  is  determined  by  the  territory  in- 
volved, is  one  that  presents  real  obstacles,  on  account  of 
the  limited  operation  attributed  to  a  cause  so  general  in 
its  nature. 

P.  W.  Latham  t  regards  some  change  in  the  nervous 
system  as  the  most  important  factor  in  the  etiology  of 
gout.  He  thinks  that  such  change  is  localised  in  the 
medulla  oblongata,  or  in  the  spinal  cord,  or  in  both,  and 
that  this  nervous  disorder  may  be  either  hereditary  or 
acquired.     He   argues    that   if   a   portion    of   the  medulla 

*  "  On  Megrim  and  Sick  Headache,"   1873,  pp.   404-405. 
t  Croonian  Lectures,  1886. 


Chap.  Ill]  CAUSATION    OF    GOUT.  57 

oblongata  involving  some  of  the  roots  of  the  vagus  be  the 
part  affected,  the  metabolism  of  the  liver  may  be  inter- 
fered with,  and  so  lead  to  the  formation  of  uric  acid.  He 
also  considers  that  if,  from  any  cause,  uric  acid  is  circulat- 
ing in  the  blood,  it  would  act  as  a  poison  upon  any  weak 
spot  in  the  nervous  system,  and  that  it  is  intelligible  that 
it  might  act  upon  portions  of  the  spinal  cord  which  control 
the  nutrition  of  the  joints,  and  so  cause  nutritive  changes 
or  inflammation  in  the  joints  connected  with  that  portion  of 
the  cord.  In  consequence  of  the  inflammation  or  nutri- 
tive changes  in  the  joints,  sodium  biurate  becomes  deposited 
in  them,  or  in  the  tissues  around  the  affected  joint.  Latham 
explains  the  phenomena  of  a  gouty  paroxysm  by  direct 
stimulation  of  sensory  nerves  by  uric  acid.  He  considers 
that  the  gout  associated  with  chronic  lead  poisoning  may 
be  explained  by  the  lead  acting,  in  such  cases,  more  particu- 
larly on  those  portions  of  the  spinal  cord  which  are  concerned 
in  gout. 

6.  Excess  of  carbonaceous  material  in  the  blood  re- 
g-arded  as  the  primary  cause  of  g'out. — Francis  Hare*  has 
put  forward  the  view  that  excess  of  carbonaceous  material 
in  the  blood,  or,  as  the  author  terms  it,  "  hyperpyraemia " 
(Gr.  TTvpela,  fuel),  is  an  essential,  though  by  no  means  the 
sole  factor  in  many  disorders,  such  as  common  paroxysmal 
neuroses,  migraine,  asthma,  epilepsy,  and  gout.  It  has 
frequently  been  shown  that  the  paroxysms  of  acute 
articular  gout  are  interchangeable  with  the  paroxysms 
of  migraine,  asthma,  and  epilepsy,  and  many  cases  have 
been  reported  in  which  the  onset  of  acute  gout  has  bcv^n 
exactly  coincident  with  the  complete  subsidence,  temporary 
or. even  permanent,  of  long-standing  migraine,  asthma,  and 
epilepsy,  and  others  marked  by  converse  substitutions. 

Hare  therefore  considers  that  it  is  reasonable  to  sup- 
pose that  the  accumulation  which  precedes,  and  the  dis- 
charge  which   accompanies,    the   acute   gouty    paroxysm, 

*  "  A  Common  Humoral  Factor  of  Disease,"   1905. 


58  GOUT:    PATHOLOGY.  [Part  i. 

are  similar  in  nature  to  the  accumulations  and  discharges 
which  occur  in  connection  with  the  migrainous,  asthmatic, 
and  epileptic  paroxysms.  He  considers  that  the  car- 
bonaceous compounds  have  a  greater  tendency  to  accumu- 
late in  the  blood  than  the  nitrogenous.  For  while  the  in- 
gestion of  proteid  food,  whether  in  small  or  large  quantities, 
is  quickly  followed  by  a  corresponding  increase  in  the 
elimination  of  nitrogenous  excreta,  such  as  urea,  there 
is  no  such  rapid  and  commensurate  increase  in  the 
elimination  of  carbonic  acid  after  the  ingestion  of  carbon- 
aceous food  ;  indeed,  the  capacity  possessed  by  the  organism 
for  increasing  catabolism  in  response  to  the  absorption  of 
an  excess  of  carbonaceous  food  is  strictly  limited.  It  is 
a  remarkable  fact  that  for  adequate  carbonaceous  cata- 
bolism the  organism  is  largely  dependent  on  muscular 
exercise  and  exposure  to  cold — conditions  which  influence 
but  slightly  nitrogenous  catabolism.  Hence  it  follows 
that  a  liberal  supply -of  carbonaceous  food,  combined  with 
deficient  exercise,  especially  in  warm  weather,  favours  an 
accumulation  of  the  carbon  contents  of  the  blood.  Such 
an  accumulation  would,  of  course,  be  precluded  by  an  ade- 
quate increase  in  the  rate  of  fat  formation,  but  the  capacity 
for  fat  formation  is  conspicuously  deficient  in  many  per- 
sons, and  may,  moreover,  have  already  attained  its  limit. 
In  these  days  of  warm  clothing,  warm  rooms,  and  little 
exercise,  when  starch  and  sugar  are  consumed  in  such  truly 
enormous  quantities,  the  conditions  are,  it  is  contended, 
all  favourable  for  the  induction  of  the  hyperpyrsemic  state. 
Hare  maintains  that  an  excessive  ingestion  of  starch  or 
sugar  may  lead  to  "  glycogenic  distension  "  of  the  liver, 
which,  by  compressing  the  intrahepatic  portal  capillaries, 
causes  mechanical  congestion  of  the  whole  retrohepatic 
portal  venous  system,  and  consequently  of  the  whole  gastric 
and  intestinal  mucosa.  Hence  digestion  and  absorption 
are  inhibited,  and  in  this  way  the  liver  tends  to  restrict 
the  whole  nutrient  income,  and  therefore  the  carbonaceous 


Chap.  Ill]        BACTERIAL   ORIGIN    OF    GOUT.  59 

income  of  the  blood.  On  the  other  hand,  undue  accumula- 
tion of  the  carbon  contents  of  the  blood  may  be  prevented 
by  an  increase  in  the  carbonaceous  expenditure  of  the  blood, 
the  main  items  of  which  are  fat  formation,  combustion  or 
carbonaceous  catabolism,  and  in  women  utero-gestation, 
lactation,  and  menstruation.  He  considers  that  hyper- 
pyraemia  may,  under  different  conditions,  culminate  in 
acute  gout,  and  that  the  pyrexia  of  acute  gout,  lasting  as 
it  may  do  many  days,  is  curative  of  the  underlying  hyper- 
pyrsemic  condition,  and  of  all  those  hyperpyraemic  manifes- 
tations (irregular  or  suppressed  gout)  which  so  often  pre- 
cede the  articular  paroxysm. 

7.  A  bacterial  toxin  regrarded  as  the  primary  cause 
of  gout. — If  the  symptoms  of  gout  are  not  due  to  uric 
acid,  yet  they  must  be  caused  by  some  other  constituent 
of  the  blood.  The  normal  constituents  of  the  blood  are 
well  known,  and  there  is  no  increase  in  any  of  them  in 
gout  sufficient  to  cause  its  symptoms  ;  so  that  it  must 
be  due  to  one  of  those  bodies,  such  as  the  toxins,  which 
we  know  to  be  present  in  many  diseases,  but  are  not  able 
to  separate  in  analyses.  In  differentiating  the  symptoms 
of  gout  it  can  be  noted  that  the  principal  symptoms 
are  similar  to  those  produced  by  toxins  in  diseases  in 
which  the  symptoms  are  caused  by  the  action  of  bac- 
terial toxins  on  the  tissues.  For  instance,  the  joints  are 
peculiarly  liable  to  be  affected  by  the  toxins  of  rheumatic 
fever,  septicsemia,  scarlatina,  and  allied  diseases,  and  an 
attack  of  inflammation  from  this  cause  is  more  likely  to  be 
attended  by  great  pain  and  constitutional  disturbance 
than  if  due  to  the  deposition  of  sodium  biurate,  which  is 
non-irritating  when  deposited  in  other  regions  of  the  body. 
The  bacterial  view  of  the  pathogenesis  of  gout  was  very 
ably  dealt  with  by  Ringrose  Gore  in  a  paper  read  before 
the  British  Medical  Association  in  1900.  In  that  paper 
the  author  stated  his  view  that  gout  was  caused  by  some 
product   of  digestion,   either  absorbed  from  the  digestive 


6o  GOUT :    PATHOLOGY.  [Part  l 

tract  or  produced  by  some  alteration  of  metabolism  going 
on  in  some  of  the  digestive  organs  ;  that  there  must  be 
some  body  formed  in  the  intestinal  canal  capable  both  of 
causing  the  symptoms  of  gout  and  also  of  so  altering  the 
metabolism  of  the  liver  as  to  cause  an  increased  formation 
of  uric  acid.  He  went  on  to  state  that  he  considered  a 
toxin  was  the  cause  of  the  disease,  a  product  of  a  definite 
bacillus,  and  a  product  of  one  of  the  bacilli  normally  found 
in  the  intestinal  canal. 

A  little  later  in  the  same  year  Le  Gendre  read  a  paper 
at  the  International  Congress  of  Medicine  in  Paris,  in 
which  he  foreshadowed  the  possible  intestinal  origin  of 
gout.  A  year  later  Chalmers  Watson  drew  attention  to 
this  view  of  the  origin  of  gout.  In  1903  there  appeared  in 
the  Lancet  a  most  instructive  paper  by  Woods-Hutchinson, 
in  which  he  stated  his  view  that  gout  was  a  toxaemia  ;  that 
the  source  of  the  toxin  was  the  gastro-intestinal  tract  ;  that 
owing  to  some  catarrhal  or  inflamed  condition  of  that  tract, 
possibly  secondary  to  some  chemical  changes  within  that 
tract,  a  toxin  was  produced  that  was  absorbed  into  the 
circulation  ;  that  if  the  cells,  either  the  wandering  leuco- 
cytes of  the  blood  and  the  lymph  or  the  fixed  body  cells, 
could  successfully  combat  and  neutralise  that  poison  nothing 
resulted.  He  thought  that  probably  such  was  the  case 
in  people  who  suffered  from  certain  intestinal  derangements 
which  quickly  passed  off  ;  but  if  the  cells  were  powerless 
completely  to  neutralise  that  toxin,  then,  as  the  result  of 
the  unaltered  toxin  that  was  circulating  in  the  blood  and 
lymph,  gout  resulted  ;  that  the  cells,  lymphocytes  and  fixed 
body  cells,  which  were  able  to  neutralise  part  of  that  toxin 
suffered  degradation  and  degeneration  in  neutralising  it, 
and  as  a  result  uric  and  phosphoric  acids,  the  debris  of 
nucleinic  substances,  were  set  free,  and  that  that  was  the 
origin  of  uric  acid  which  in  certain  cases  might  be  deposited 
as  an  after-effect  in  the  form  of  sodium  biurate. 

The  selective   action  of  toxins  on  different  tissues  is 


Chap.  III.]        BACTERIAL    ORIGIN    OF    GOUT.  6i 

exampled  by  the  way  in  which  cartilaginous  and  fibrous 
structures  become  inflamed  in  gout.  These  tissues  are 
also  more  liable  or  earlier  liable  on  account  of  their  lower 
vitality.  As  gout  becomes  more  advanced  the  higher  struc- 
tures become  involved  and  various  nervous  symptoms 
occur,  such  as  some  of  the  cardiac  attacks,  which  are  cer- 
tainly toxic  in  character  ;  the  various  tissues  and  organs 
affected  by  gout,  the  inflamed  joints,  the  kidney  disease, 
eczema,  catarrh,  and  inflammation  of  the  various  mucous 
membranes,  gastritis,  phlebitis,  neuritis,  cardiac  gout,  form 
a  group  which  have  marked  toxic  analogies,  and  can  be  best 
explained  by  the  action  of  a  toxin  circulating  in  the 
blood. 

If  the  toxin  which  produces  gout  is  formed  by  one  of 
those  bacilli  normally  found  in  the  intestinal  canal,  the 
formation  of  the  toxin  must  be  due  to  some  pathogenic 
alteration  in  the  character  of  the  bacillus,  which  might  be 
accomplished  either  by  a  change  in  the  intestinal  secretion 
or  by  a  marked  alteration  in  the  amount  or  character  of  the 
food.  While  the  intestinal  bacteria  may  be  non-pathogenic 
under  normal  conditions,  a  slight  change  in  environment 
may  make  a  great  alteration  in  this  respect,  and  the  most 
common,  such  as  the  Bacillus  coli  communis,  may  produce 
the  most  virulent  toxins.  This  is  well  seen,  as  Treves  has 
pointed  out,  in  acute  intestinal  obstruction,  where  a  change 
takes  place  in  the  intestinal  secretion,  the  intestinal  bac- 
teria becoming  virulent  ;  and  the  patient  may  die  of  acute 
peritonitis,  with  acute  toxic  poisoning,  and  no  bacteria 
other  than  those  normally  present  in  the  intestines  may  be 
found.  In  appendicitis,  again,  the  Bacillus  coli  communis 
may  be  the  only  bacillus  present. 

The  causes  that  influence  the  growth  of  bacteria  in 
the  intestinal  canal  are  in  the  main  identical  with  those 
that  produce  gout.  For  instance,  the  quantity  of  bacteria 
in  the  intestinal  canal  varies  directly  with  the  amount  of 
proteid  food,   and  any  articles  of  food  which  produce  a 


62  GOUT:    PATHOLOGY.  [part  i. 

dyspeptic  condition  in  the  stomach  or  intestine  also  cause 
a  very  great  increase  in  the  number  of  bacteria  found  in 
the  intestinal  canal. 

Gore's  view  is  that  gout  is  probably  produced  originally 
by  an  altered  gastro-intestinal  secretion,  which  in  its  turn 
leads  to  an  alteration  of  the  toxins  produced  by  one  of  the 
intestinal  bacilli.  A  catarrhal  condition  of  the  intestinal 
mucosa  is  probably  responsible  for  the  change  in  the  intes- 
tinal secretion,  and  this  catarrhal  condition  may  be  either 
an  inherited  trait,  or  induced  by  errors  in  diet.  This 
change  in  the  intestinal  secretion  would  produce  a  change 
in  intestinal  toxins  until  a  point  would  be  reached  when  an 
excess  of  food  or  alcohol  would  generate  a  sufficient  amount 
of  toxin  to  produce  an  attack  of  gout  ;  this  tendency  would 
increase  unless  kept  in  check  by  careful  dieting,  and  subse- 
quent attacks  would  be  more  easily  produced  ;  also  this 
tendency  would  be  transmitted  to  the  offspring,  and  those 
starting  life  with  it  would  tend  to  have  gout  earlier,  and  in 
an  aggravated  form. 

Woods-Hutchinson  regards  uric  acid  as  purely  a  symp- 
tom or  index  of  certain  changes  taking  place  in  the  body 
metabolism,  and  defines  gout  as  a  toxaemia  of  varying 
causation,  usually  of  gastro-intestinal  origin,  accompanied 
by  the  formation  of  an  excess  of  urates,  this  excess  of  urates 
being  due  to  the  breaking  down  of  the  leucocytes  and  fixed 
cells  in  the  attempt  to  neutralise  the  poison  ;  in  other 
words,  being  the  measure  of  the  resisting  power  of  the  body 
tissues.  The  formation  and  introduction  of  the  toxins  are 
by  no  means  confined  to  the  gouty  ;  it  is  only  the  nature 
of  the  resistance  of  the  body  to  them  that  gives  the  charac- 
ter of  gout.  The  exciting  cause  of  gout  may  be  the  toxin  of 
micro-organisms  acting  directly  or  indirectly,  or  an  auto-in- 
toxication from  deficient  digestion  or  metabolism.  In  many 
cases  the  exciting  cause  may  to  some  extent  be  discovered 
— such,  for  instance,  as  intestinal  fermentation  or  putre- 
faction, or  some  disorder  of  the  teeth,  or  mouth,  or  stomach. 


Chap.  III.]       BACTERIAL    ORIGIN    OF    GOUT.  63 

So  far,  it  cannot  be  said  that  any  bacterium  specific  of 
gout  has  been  discovered. 

Trautner  *  regards  a  mucous  coHtis  as  one  of  the  first 
manifestations  of  gout,  and  considers  that  the  Bacillus 
coli  communis  is  the  initial  agent  in  gouty  affections.  He 
states  that  the  Bacillus  coli  communis  produces  a  reducing 
substance,  which  is  transformed  into  xanthin  and  uric  acid 
during  its  passage  through  the  body.  It  is  fairly  well 
known  that  different  species  of  intestinal  bacteria  secrete 
or  excrete  substances  which  restrict  the  growth  of  other 
species,  and  sometimes  of  their  own.  At  the  same  time, 
the  intestinal  mucosa  pours  forth  secretions,  which  also 
materially  affect  the  bacteria  or  their  products,  so  that  the 
degree  of  the  intestinal  infection  in  gout  must  depend  in 
part  upon  the  species  of  bacteria  present,  and  in  part  upon 
the  integrity  of  the  secreting  cells  of  the  intestinal  mucosa. 
No  doubt  hereditary  deficiency  in  the  digestive  faculties  may 
be  responsible  for  the  production  of  exceptionally  power- 
ful toxins,  or  may  diminish  the  resistance  to  the  products  of 
the  intestinal  bacteria. 

It  has  been  customary  to  regard  the  bacillus  coli  group 
as  the  most  characteristic  intestinal  bacteria,  but  Houston 
has  shown  that  streptococci  surpass  the  colon  bacilli  in  abund- 
ance in  normal  human  f?eces  ;  they  were  at  times  present 
to  the  number  of  1,000,000,000  per  gramme.  Streptococci 
are  thus  present  in  the  intestine  of  man,  and  of  such  animals 
as  have  been  examined,  in  vast  numbers,  exceeding,  in 
most  cases,  all  other  bacteria.  Andrewes  has  brought  for- 
ward evidence  to  show  that  the  streptococci  are  well- 
established  saprophytes  of  the  alimentary  canal,  and  that 
to  all  intents  and  purposes  they  are,  at  the  present  day,  ex- 
clusively attached  to  the  animal  body,  and  in  particular  to 
the  alimentary  canal.  Here,  and  here  alone,  they  flourish 
and  prevail  in  incredible  numbers.  Andrewes  and  Horder 
have  recently  published  the  details  of  the  examination  of 

*  Nord.  Med.  Arkiv.,  1905. 


64  GOUT:    PATHOLOGY.  [Part  i. 

more  than  two  hundred  strains  of  streptococci  from  cases 
of  human  disease. 

In  my  opinion,  the  view  that  a  bacterial  toxin  is  the 
primary  cause  of  gout  is  the  most  probable  one.  In  a 
former  edition  of  this  book  I  supported  the  theory  as  to  the 
renal  origin  of  the  disease,  but  recent  advances  in  our 
knowledge  of  the  pathology  of  gout  have  led  me  to  abandon 
that  theory.  The  view  as  to  the  bacterial  origin  of  gout  is 
supported  by  the  well-known  fact  that  adequate  removal 
of  the  intestinal  contents  at  the  commencement  of  the 
gouty  attack  always  effects  rapid  diminution  of  the  symp- 
toms. Moreover,  the  classic  remedies  for  gout  have  only 
two  things  in  common  :  one  that  they  relieve  gout,  and 
the  other  that  they  check  intestinal  putrefaction,  or  diminish 
the  absorption  of  its  products,  or  promote  their  elimina- 
tion from  the  system. 

It  must  be  remembered  that  there  are  two  drugs  which 
from  their  great  influence  in  gout  must  always  be  taken 
into  consideration  when  thinking  of  the  origin  of  this  disease 
■ — the  action  of  colchicum  in  relieving  and  that  of  lead  in 
inducing  gout.  It  is  suggestive  that  both  have  an  action  on 
the  intestinal  secretion  :  colchicum  causes  an  immediate 
alteration  in  its  amount  and  character  ;  lead  has  the 
opposite  effect  of  causing  a  diminution  and  alteration  of 
the  intestinal  secretion  when  taken  in  small  and  long- 
continued  doses. 

The  liver  as  a  toxin  destroyer.^ One  of  the  most 
important  functions  possessed  by  the  liver  is  that  of  a 
toxin  destroyer,  or  poison  filter,  for  the  blood  in  general, 
and  that  of  the  portal  system  in  particular.  Attention 
to  this  was  first  attracted  by  the  discovery  that  extirpa- 
tion, or  ligation,  of  the  blood-vessels  of  the  liver  in  the  lower 
vertebrates  was  promptly  followed,  not  by  mere  impair- 
ment of  digestive  power,  but  by  a  rapidly  fatal  group  of 
toxic  symptoms  similar  to  those  of  acute  poisoning,  end- 
ing in    coma,  with   or  without   convulsions,  and  in  death. 


Chap.  III.]  THE    LIVER    AND    TOXINS.  65 

The  experiment  was  carried  a  step  further,  and  the  blood 
from  the  portal  vein  diverted,  by  means  of  a  fistula,  directly 
into  the  vena  cava,  without  passing  through  the  liver  ; 
and  again  symptoms  of  acute  intoxication  developed, 
which  soon  proved  fatal,  although  less  rapidly  than  when 
the  hepatic  artery,  or  vein,  was  also  tied.  The  blood  was 
taken  from  the  portal  vein  of  one  rabbit,  and  injected  into 
the  tissues  of  another,  and  found  to  be  markedly  toxic  ; 
while  that  drawn,  under  similar  conditions,  from  the  vena 
cava  on  the  cardiac  side  of  the  liver  was  found  to  be  only 
very  mildly  so.  The  conclusion  was  arrived  at,  some  ten 
or  twelve  years  ago,  that  the  most  important  and  essential 
function  of  the  liver  was  that  of  a  reducer  and  detoxicator 
of  toxic  substances,  contained  both  in  the  portal  and  in 
the  (hepatic)  arterial  blood. 

According  to  this  view,  the  role  of  the  liver  in  gout  is 
a  negative  one,  being  inability  to  perform  its  chief  normal 
functions  of  acting  as  a  "  poison  filter  "  and  of  absorbing 
or  transforming  into  harmless  excretory  substances  the 
excess  of  toxins  brought  to  it  by  the  f)ortal  vein. 


CHAPTER    IV. 

ALKALINITY   OF   THE   BLOOD   IN   GOUT. 

Uric  acid  a  normal  constituent  of  the  blood — Diseases  associated 
with  an  excess  of  uric  acid  in  the  blood — Alkalinity  of  the 
blood  in  gout — Alkalinity  of  the  blood  and  the  precipitation 
of  sodium  biurate. 

Uric  acid  a  normal  constituent  of  the  blood.— It  will 
be  evident  that  if  uric  acid  is  not  formed  in  the  kidneys 
it  must  be  brought  to  those  organs  in  the  blood  in  some 
combination  or  other. 

We  know  "that  some  400-500  grains  of  urea  are  nor- 
mally excreted  in  the  urine,  and  that  this  urea  is  conveyed 
in  the  blood  from  various  organs  to  the  kidneys,  where  it 
is  excreted.  But,  in  addition,  from  eight  to  ten  grains  of 
uric  acid  are  daily  excreted  in  the  urine  of  man.  The 
question  is,  does  this  uric  acid  come  as  such  to  the  kidneys  ? 
In  other  words,  is  it  produced  in  any  of  the  organs  or 
tissues  of  the  body  generally  and  conveyed  in  the  blood  to 
the  kidneys,  to  be  by  them  excreted,  or  is  it  produced  in 
the  kidneys  and  then  turned  into  the  urine  ?  The  answers 
to  these  questions  will  depend  very  much  upon  our  ascer- 
taining whether  uric  acid  exists  in  the  blood  of  man  in 
health,  and  whether  it  exists  in  the  blood  of  those  animals, 
such  as  birds,  the  whole  of  whose  nitrogenous  urinary 
excrement  consists  of  a  compound  of  uric  acid.  For  it 
follows  that  if  uric  acid  be  not  formed  in  the  kidneys,  it 
must  be  conveyed  in  the  blood  to  those  organs.  If  such  be 
the  case,  its  detection  in  the  blood,  provided  careful  search 
for  it  be  made,  ought  to  be  a  fairly  easy  matter,  considering 

66 


Chap.  IV.]  URIC    ACID    IN    BLOOD.  67 

that  in  the  murexide  reaction  we  have  such  an  extremely 
delicate  test  for  the  identification  of  uric  acid. 

Here  it  is  well  to  bear  in  mind  that  statements  as  to 
the  presence  of  uric  acid  in  the  blood  and  viscera  are  value- 
less unless  the  substance  is  proved  to  be  uric  acid  by  the 
murexide  test.  Haig,  who  asserts  that  uric  acid  is  always 
present  in  the  blood  and  tissues,  bases  his  statements  solely 
on  the  application  of  Haycraft's  process  to  water-extracts 
of  the  blood  and  tissues,  and  the  subsequent  calculation  of 
the  silver  precipitate  so  obtained  in  terms  of  uric  acid. 
As  far  as  can  be  ascertained  from  Haig's  writings,  he  has 
never  identified  by  the  murexide  test  this  uric  acid  reported 
to  be  present  in  the  blood  and  tissues. 

Garrod's  thread  test: — Garrod's  thread  test  is  a  rough 
method  for  the  detection  of  uric  acid  in  the  blood,  and  is 
performed  as  follows  : — To  two  drachms  of  serum  obtained 
from  a  blister  (apphed  at  a  site  other  than  the  inflamed 
spot)  add  ten  to  twelve  drops  of  strong  acetic  acid.  Mix 
the  two  fluids,  and  immerse  one  or  two  linen  threads, 
and  set  aside  for  twenty-four  hours.  Then  examine 
with  a  low  power  of  the  microscope,  and  if  a  positive 
result  is  attained,  numerous  minute  rhombic  crystals  of 
uric  acid  will  be  found  on  the  submerged  part  of  the 
thread. 

As  a  matter  of  fact,  the  detection  of  small  quantities  of 
uric  acid  in  the  blood  is  a  more  difficult  matter  than  was 
originally  thought  to  be  the  case. 

Sir  Alfred  Garrod,*  as  the  result  of  his  investigations, 
declares  that  in  absolute  health  the  uric  acid  in  the  blood 
is  inappreciable,  that  in  gout  the  blood  is  very  rich  in  it, 
and  that  uric  acid  is  found  in  smaller  but  appreciable 
quantities  in  individuals  who  are  developing  a  gouty  con- 
dition, or  who  are  under  the  poisonous  influence  of  lead. 
Von    Jaksch  f    examined    the    blood    of    several    healthy 

*  Lumleian   Lectures,    1883. 

t  Deut.  medicin.   Woch.,   1890,  xxxiii.,  p.   741. 


68  GOUT:    PATHOLOGY.  [Part  i. 

individuals,  but  found  no  uric  acid  present.  Klemperer  * 
also  was  unable  to  find  any  uric  acid  in  the  blood  of 
healthy  persons.  I  too  have  examined  the  blood  of 
healthy  subjects  without  being  able  to  find  uric  acid. 

Sir  Alfred  Garrod  examined  the  blood  of  the  ox,  sheep, 
and  pig  by  the  uric  acid  thread  test,  but  could  never  find 
a  trace  of  uric  acid  present. 

The  examination  of  the  blood  of  "birds  and  reptiles  has 
a  very  important  bearing  on  the  discovery  of  the  normal 
seat  of  formation  of  uric  acid.  As  is  well  known,  the  semi- 
solid urinary  excrement  of  birds  consists,  apart  from  the 
small  quantity  of  water  present,  entirely  of  uric  acid  com- 
pounds, so  that  the  nitrogen  excreted  by  the  kidneys  of 
birds  is  eliminated  entirely  in  the  form  of  uric  acid  and  none 
of  it  in  the  form  of  urea.  This  white  mortar-like  urinary 
excrement  of  birds  has  been  shown  by  Sir  William  Roberts 
to  consist  of  the  quadriurates  of  ammonium,  potassium,  and 
sodium.  Consequently  birds  excrete  in  proportion  to 
their  body-weight  an  enormous  amount  of  uric  acid  as  com- 
pared with  the  uric  acid  output  of  mammals.  If  this  large 
quantity  of  uric  acid  be  produced  in  the  organs  and  tissues 
generally  it  must  be  conveyed  in  the  blood  to  the  kidneys, 
and  it  therefore  should  be  capable  of  detection  in  the 
blood  of  birds.  It  has,  however,  until  comparatively  re- 
cently, escaped  detection. 

Sir  Alfred  Garrod  examined  the  blood  of  the  turkey, 
fowl,  pigeon,  and  duck  by  the  uric  acid  thread  test,  but 
never  found  a  trace  of  uric  acid  present. 

I  also  have  worked  on  the  blood  of  the  turkey,  goose, 
duck,  and  fowl,  but  have  never  been  able  to  detect  any 
uric  acid  in  the  blood  of  those  birds. 

John  Davy  examined  the  blood  of  two  snakes  [Viper 
communis)  for  uric  acid,  but  failed  to  detect  any. 

Chalmers  Watson,  using  a  more  improved  method  of 
extraction,  has  been  able  to  detect  uric  acid  in  the  blood 

*  Deut.  medicin,  Woch.,  1895,  xxi.,  p.  655. 


Chap.  IV.  URIC    ACID    IN    BLOOD.  69 

of  the  duck,  goose,  and  turkey.  It  must,  therefore,  be 
concluded  from  the  results  of  his  experiments  that  uric 
acid  is  normally  present  in  the  blood  of  birds. 

Croftan  also  states  that  he  has  found  uric  acid  in  the 
blood  of  twelve  normal  subjects,  and  Petren  has  also  found 
it  in  the  blood  of  healthy  human  beings  in  very  small  quan- 
tities. It  must,  therefore,  I  think,  be  conceded  that  the 
uric  acid  excreted  by  the  kidneys  in  the  urine  is  brought 
to  those  organs  in  the  blood. 

Other  diseases  associated  with  an  excessive  amount 
of  uric  acid  in  the  blood.^ — Apart  from  gout,  an  excess 
of  uric  acid  has  been  detected  in  the  blood  in  the  follow- 
ing diseases  : — Primary  and  secondary  anaemia,  pernicious 
anaemia,  splenic  tumours,  leukaemia,  pneumonia,  malignant 
disease,  chronic  Bright's  disease,  contracted  granular  kid- 
ney, ulcerative  endocarditis,  acute  aneurism,  gonorrhoeal 
rheumatism,  plumbism,  intestinal  inflammation,  malaria, 
and  typhus  (after  the  febrile  stage). 

Von  Jaksch  *  found  uric  acid  in  the  blood  of  cases  of 
both  primary  and  secondary  anaemia,  pernicious  anaemia, 
and  splenic  tumour.  He  also  found  it  in  the  blood  in  con- 
ditions inducing  dyspnoea,  notably  in  heart  disease,  pleurisy 
with  effusion,  pulmonary  catarrh,  pneumonia,  and  emphy- 
sema. Klemperer  f  has  recently  confirmed  the  results 
of  Von  Jaksch  and  others  as  to  the  presence  of  uric  acid  in 
the  blood  of  leukaemia,  and  many  observations  have  been 
made  of  the  increased  excretion  of  uric  acid  that  accom- 
panies this  disease.  Laache  J  found  a  daily  excretion  of 
3.7  grammes  (nearly  six  times  the  average  normal  amount) 
in  a  patient  suffering  from  this  disease.  Bartels  §  observed 
a  daily  excretion  of  4  grammes  (more  than  six  times  the 
average    normal    amount).       Stadthagen  ||    found    a    daily 

*  Deut.  medicin.  Woch.,  1890,  xxxiii. 
t  Deut.  medicin.   Woch.,   1895,  xxi. 
'    ■  J  "  Klin.  Urinanalyse,"  1892. 

§   Deut.   Arch.  f.  klin.   Medicin,   Bd.  i.  ' 

II   Virchow's  Arch.,  Bd.  cix. 


70  GOUT:    PATHOLOGY.  [parx  i. 

excretion  of  2  grammes  (three  times  the  average  normal 
amount).  Bohland  and  Scherz  *  found  a  daily  excretion 
of  1.4  gramme  (twice  the  average  normal  amount). 

Von  Jaksch  found  uric  acid  in  the  blood  of  all  the  cases  of 
renal  disease  that  he  examined,  the  proportions  being  especi- 
ally large  in  cases  of  granular  kidney  disease  and  uraemia. 
Von  Jaksch's  results  were  confirmed  by  Klemperer,  who 
examined  the  blood  of  cases  of  contracted  kidney  and  found 
uric  acid  always  present. 

Chalmers  Watson  has  recorded  the  results  of  an  investi- 
gation of  the  blood  in  cases  of  pneumonia,  malignant 
disease,  chronic  Bright's  disease,  ulcerative  endocarditis, 
and  acute  aneurism,  in  all  of  which  the  presence  of  uric 
acid  could  be  determined  in  the  limited  quantity  of  blood 
examined. 

Alkalinity  of  the  blood  in  grout.— It  is  remarkable 
that  for  a  very  long  time  the  view  has  been  generally  held 
that  a  diminished  alkalinity  of  the  blood  is  associated 
with  gout.  This  view,  which  is  a  pure  hypothesis,  probably 
originated  in  the  assumption  that  gout  is  associated  with 
an  acid  dyscrasia,  and  that  absorption  of  uric  acid  into  the 
blood  necessarily  diminished  the  alkalinity  of  that  medium. 
The  hypothesis  has  probably  been  strengthened,  although 
erroneously,  by  the  fact  that  the  gouty  paroxysm  is  usually 
accompanied  by  increased  acidity  of  the  urine.  Conse- 
quently some  observers  have  drawn  the  conclusion  that 
an  increased  acidity  of  the  urine  must  necessarily  be  asso- 
ciated with,  and  an  index  of,  a  diminished  alkalinity  of 
the  blood  (it  is  scarcely  necessary  to  remark  that  there  can 
be  no  such  condition  as  acidity  of  the  blood). 

The  test  of  experimental  investigation,  however,  shows 
that  the  association  of  a  diminished  alkalinity  of  the  blood 
with  gout  is  erroneous.  Klemperer  some  years  ago  proved 
by  actual  determinations  of  the  blood  of  gouty  subjects 
that  the  alkalinity  was  not  below  that  of  healthy  blood. 

■  *  Pfliiger's  Arch.,  Bd.  xlvii. 


Chap,  iv.]  ALKALINITY    OF    BLOOD.  71 

Later  on  Adolf  Magnus-Levy  found  that  there  was  no 
diminution  of  the  alkahnity  of  the  blood  during  attacks 
of  gout,  nor  was  any  obvious  difference  observed  during 
and  apart  from  the  attacks.  The  alkalinity  was  found  to 
be  much  the  same  in  healthy  and  gouty  persons,  and  both 
exhibited  fluctuations  of  alkalinity.  More  recently  I 
have  made  a  number  of  determinations  of  the  alkalinity 
of  the  blood  of  healthy  and  gouty  persons' — using  the  deli- 
cate process  devised  by  A.  E.  Wright,  which  only  requires 
the  abstraction  of  three  or  four  drops  of  blood  from  the 
individual-— with  the  result  that  so  far  I  have  found  in  every 
gouty  patient  whose  blood  I  have  examined  a  higher  al- 
kalinity than  the  average  alkalinity  of  the  blood  of  healthy 
persons.  The  results  that  I  have,  up  to  the  present  time, 
obtained  show  that  whereas  the  alkalinity  of  the  blood  of 
healthy  adults  varies  from  0.161  to  0.185  per  cent,  of  anhy- 
drous sodium  carbonate,  with  an  average  of  0.167  P^^"  cent., 
the  alkalinity  of  the  blood  of  gouty  patients  varies  from 
0.193  to  0.251  per  cent.,  with  an  average  of  0.217, 
which  is  nearly  one-third  higher  than  that  of  normal 
blood. 

It  is  well  known  that  an  attack  of  gout  may  be  acceler- 
ated by  ingestion  of  food  or  beverages  harmful  either  as 
regards  their  quality  or  quantity.  Such  substances  may 
exert  a  direct  or  indirect  chemical  action  which  facilitates 
the  precipitation  of  sodium  biurate- — this  is  the  chemical 
view— or  they  may  possibly  exert  a  physical  action  only 
in  hastening  such  precipitation' — this  is  the  mechanical  view. 
A  view  which  is  commonly  held  as  to  the  influence  of  diet 
and  certain  beverages  in  accelerating  an  attack  of  gout,  is 
that  such  substances  reduce  the  alkalinity  of  the  blood,  and 
so  hasten  the  precipitation  of  sodium  biurate.  It  is  re- 
markable what  a  number  of  writers  incline  to  the  view 
that  diminution  of  the  alkalinity  of  the  blood  causes  the 
deposition  from  it  of  sodium  biurate,  and  that  a  subsequent 
rise  in  alkalinity  causes  solution  of  the  previously  formed 


72  GOUT:    PATHOLOGY.  [part  i. 

deposits.  It  is  assumed  that  a  nitrogenous  animal  diet 
diminishes  the  alkahnity  of  the  blood  and  so  causes  de- 
position of  sodium  biurate.  It  is  also  assumed  that  a 
similar  result  is  caused  by  the  acids  contained  in  wines 
and  beers  ;  and  that  the  pains  in  the  joints  that  frequently 
occur  in  gouty  subjects  soon  after  taking  certain  wines 
or  beers  are  due  to  deposition  of  biurate  following  on 
the  reduction  of  the  alkalinity  of  the  blood  by  the  acid 
so  introduced. 

Now,  I  have  been  unable  to  meet  with  any  experimental 
proof  that  a  diminution  in  the  alkalinity  of  blood  con- 
taining uric  acid  in  solution  either  facilitates  the  depo- 
sition of  sodium  biurate  from  it,  or  diminishes  its  solvent 
power  for  sodium  biurate  or  for  uric  acid.  I  therefore 
considered  it  advisable  experimentally  to  investigate  these 
different  points,  and  for  that  purpose  the  following  series 
of  experiments  were  undertaken. 

Experiments  showing  to  what  extent  the  rate  of  forma- 
tion and  precipitation  of  sodium  biurate  is  affected  by 
diminishing,  by  the  addition  of  acids,  the  alkalinity  of 
blood  serum  charged  with  uric  acid: — Seven  bottles,  each 
containing  40  c.c.  of  blood  serum,  were  raised  to  100°  F., 
and  then  charged  with  uric  acid  to  the  extent  of  i  in  1,000. 
As  soon  as  the  uric  acid  was  dissolved,  varying  quantities 
of  hydrochloric  acid  were  added  to  the  contents  of  three 
of  the  bottles,  and  of  tartaric  acid  to  another  three,  so 
as  partially  to  reduce  the  alkalinity  of  the  serum  ;  the 
contents  of  the  seventh  bottle  were  left  unaltered.  The 
bottles  were  kept  in  a  warm  chamber  at  100°  F.,  and  the 
commencement  of  the  precipitation  of  sodium  biurate 
crystals  was  then  looked  for  by  examining  some  of  the 
contents  of  the  bottles  under  the  microscope  every  few 
minutes,  so  as  to  note  the  time  when  the  formation  of 
biurate  crystals  commenced.  The  quantities  of  hydro- 
chloric acid  added  to  the  contents  of  three  of  the  bottles 
were  such  as  to  neutralise  respectively  three-fourths,  one- 


Chap.  IV.] 


ALKALINITY    OF    BLOOD. 


73 


half,  and  one-fourth  of  the  alkahnity  of  the  scrum  remain- 
ing after  solution  of  the  uric  acid.  To  the  other  three 
bottles  corresponding  quantities  of  tartaric  acid  were 
added  to  produce  similar  results.  The  following  tables 
(Table  III.  and  Table  IV.)  show  the  results  of  these  ex- 
periments. 

TABLE    III. 

Results  of  experiments  made  with  blood  serum  charged  with  uric  acid, 
to  show  the  effect  ivhich  the  diminution  of  the  alkalinity  of  the 
serum,  by  the  addition  of  hydrochloric  acid,  has  on  the  precipitation 
of  sodium  biurate. 


Solution. 


Commencement  of  precipitation. 


Blood    serum    containing    i    in 
1,000   uric  acid. 

The   same,    one-fourth   neutral- 
ised by  hydrochloric  acid. 

The  same,   one-half  neutralised 
by  hydrochloric   acid. 

The  same,  three-fourths  neutral- 
ised by  hydrochloric  acid. 


Crj^stals  of  sodium  biurate  first 
appeared  in  6-j  hours. 

Do. 


Do. 


Some  crystals  of  uric  acid  ap- 
peared in  5  minutes.  Crys- 
tals of  sodium  biurate  first 
appeared  in  12  hours. 


It  will  be  seen  from  the  results  of  these  experiments 
that  the  effect  of  diminishing  the  alkalinity  of  blood  serum 
as  far  as  one-half  has  no  influence  whatever  in  hastening 
the  conversion  of  the  sodium  quadriurate  into  biurate, 
or,  in  other  words,  does  not  influence  the  deposition  of 
sodium  biurate  from  the  serum.  When  the  alkalinity  is 
reduced  by  three-fourths,  by  the  addition  of  hydrochloric 
acid,  some  crystals  of  uric  acid  were  almost  immediately 
precipitated,  but  when  this  precipitation  of  uric  acid  had 
ceased,  then  the  deposition  of  sodium  biurate  did  not 
begin  till  twelve  hours  had  elapsed.     The  reason  that  the 


74 


GOUT:    PATHOLOGY. 


[{■Art  1. 


deposition  of  sodium  biurate  was  delayed  a  longer  time 
than  in  the  cases  of  the  serum,  the  alkalinity  of  which 
was  reduced  respectively  by  one-fourth  and  one-half,  was 
that  the  removal  of  some  of  the  uric  acid  rendered  the 
solution  of  sodium  quadriurate  weaker,  and,  as  has  been 
pointed  out  by  Sir  WiUiam  Roberts,  the  amount  of  uric 
acid  in  solution  exercises  a  very  important  influence  on 
the  rate  of  maturation  of  the  quadriurate,  and  the  advent 
of  precipitation  of  the  biurate.  This  early  shower  of  uric 
acid  crystals  that  occurred  when  sufficient  hydrochloric 
acid  was  added  to  the  blood  serum  to  neutralise  three- 
fourths  of  its  alkalinity  has  no  bearing  whatever  on  the 
chemistry  of  the  gouty  attack,  since  the  gouty  deposit 
always  consists  of  sodium  biurate,  and  never  of  uric  acid. 
The  following  table  shows  the  results  of  the  experiments 
obtained  with  blood  serum,  the  alkalinity  of  which  was 
partially  reduced  by  means  of  tartaric  acid. 

TABLE    IV. 

Results  of  experiments  made  with  blood  serum,  charged  with  uric  acid, 
to  show  the  efject  ivhich  the  diminution  of  the  alkalinity  of  the 
serum,  by  the  addition  of  tartaric  acid,  has  on  the  precipitation 
of  sodium  biurate. 


Solution. 


Commencement  of  precipitation. 


Blood    serum    containing    i    in 
1,000  uric  acid. 

The  same,   one-fourth  neutral- 
ised by  tartaric   acid. 

The  same,  one-half  neutralised 
by  tartaric  acid. 

The  same  three-fourths  neutral- 
ised bv  tartaric  acid. 


Crystals  of  sodium  biurate  first 
appeared  m  6-7  hours. 

Do. 


Do. 


Do. 


From  these  experiments  it   is  evident  that  even   the 
reduction  of  the  alkalinity  of  blood  serum  by  three-fourths 


Chap,  iv]  ALKALINITY    OF    BLOOD.  75 

has  no  influence  in  hastening  the  precipitation  of  sodium 
biurate  from  blood  serum  impregnated  with  uric  acid. 
The  view,  therefore,  that  a  diminution  of  the  alkaUnity 
of  the  blood  promotes  an  attack  of  gout  by  favouring  the 
deposition  of  sodium  biurate  is,  in  my  opinion,  untenable. 
In  order  to  give  an  idea  of  the  amount  of  acid  that  would 
be  required  to  reduce  the  alkalinity  of  the  blood  of  an 
adult  human  being  by  three-fourths,  I  made  the  following 
estimation  and  calculation.  I  found  that  the  acidity  of 
some  1847  port,  reckoned  as  tartaric  acid,  was  equal  to 
six  grains  of  acid  to  the  wineglassful.  In  order  to  neutralise 
three-fourths  of  the  alkalinity  of  the  blood  serum  of  a 
man  of  average  weight,  it  would  be  necessary  that 
all  the  acid  contained  in  two  bottles  of  such  port 
should  be  introduced  at  one  moment  into  the  circula- 
tion. 

Experiments  to  show  the  solvency  of  uric  acid  in  blood 
serum  the  alkalinity  of  which  has  been  reduced  by  the 
addition  of  an  acid. — The  effect  of  hydrochloric  and 
tartaric  acids  respectively  was  investigated.  As  will  be 
seen  from  the  results,  there  is  a  remarkable  difference 
in  the  solvent  power  of  partially  neutralised  blood  serum 
for  uric  acid,  accordingly  as  its  alkalinity  is  reduced  by 
the  addition  of  hydrochloric  or  tartaric  acid.  The  ex- 
periments were  carried  out  in  the  following  manner  : — 
Four  bottles  each  containing  25  c.c.  of  blood  serum  were 
taken  ;  three  of  them  were  treated  respectively  with  differ- 
ent quantities  of  hydrochloric  acid,  so  as  to  reduce  the 
alkalinity  of  the  serum  in  one  case  by  one-fourth,  in  the 
second  case  by  one-half,  and  in  the  third  case  by  three- 
fourths  ;  the  contents  of  the  remaining  bottle  were  left 
untouched.  The  bottles  were  placed  in  the  warm  chamber 
till  their  contents  were  at  100°  F.,  and  then  an  excess 
(60- — 70  milligrammes)  of  uric  acid  was  added  to  each. 
They  were  kept  in  the  warm  chamber  for  two  hours,  during 
which  time  they  were  frequently  agitated  ;  the  contents  of 


76 


GOUT:    PATHOLOGY. 


[Part  1. 


the  bottles  were  then  filtered  from  undissolved  uric  acid, 
and  the  dissolved  uric  acid  in  each  filtrate  was  estimated. 
The  following  table  shows  the  results  : — 

TABLE    V. 

Showing  the  solubility  of  uric  acid  at  lOo''  F.  in  unaltered  blood  seyum 
and  in  blood  serum  the  alkalinity  of  ivhich  is  proportionately 
reduced  by  the  addition  of  hydrochloric  acid. 


Solvent. 

Uric  acid  dissolved. 

Unaltered  serum 

Serum  one-fourth  neutralised  by  hydrochloric 
acid 

Serum  one-half  neutralised  by  hydrochloric  acid 

Serum  three-fourths    neutralised    by  hydro- 
chloric acid 

2.03  per   1,000. 
1.48 

I. GO 

0.45 

Similar  experiments  were  carried  out  using  tartaric  acid 
in  the  place  of  hydrochloric  acid.  The  results  were  as 
follows  :■ — 

TABLE   VI. 

Showing  the  solubility  of  uric  acid  at  100°  F.  in  unaltered  blood  serum 
and  in  blood  serum  the  alkalinity  of  which  is  proportionately 
reduced  by  the  addition  of  tartaric  acid. 


Solvent. 


Uric  acid  dissolved. 


Unaltered  serum 

Serum  one-fourth  neutralised  by  tartaric  acid 

Serum  one-half  neutralised  by  tartaric  acid 

Serum   three-fourths   neutralised   by   tartaric 
acid 


2.03  per  1,000 
2.01  ,, 

2.01  ,, 

2.02 


Chap.  IV.]  ALKALINITY    OF    BLOOD.  -j'] 

It  is  seen  from  the  results  of  these  experiments  that 
if  the  alkahnity  of  blood  serum  is  reduced  by  the  addition 
of  hydrochloric  acid,  the  solvency  of  the  serum  for  uric 
acid  is  correspondingly  altered.  This  is  what  would  be 
expected,  since  the  conversion  of  some  of  the  sodium 
bicarbonate  of  the  serum  into  sodium  chloride  renders 
that  portion  of  the  sodium  unattainable  by  the  uric  acid, 
and  prevents  the  solution  of  a  corresponding  amount  of 
the  latter  as  sodium  quadriurate.  Such  a  result,  how- 
ever, does  not  follow  the  reduction  of  the  alkalinity  of 
the  serum  by  the  addition  of  an  organic  acid,  such  as 
tartaric  acid.  It  will  be  seen  that  serum,  the  alkalinity 
of  which  is  reduced  respectively  by  one-fourth,  one-half, 
and  three-fourths,  practically  does  not  vary  at  all  as  regards 
its  solvency  for  uric  acid.  The  explanation,  no  doubt, 
is  that  the  uric  acid  is  able  to  displace  the  tartaric  acid 
from  its  combination  with  sodium,  and  utilise  the  sodium 
of  the  tartrate  as  readily  as  the  sodium  of  the  bicarbonate 
to  form  the  soluble  sodium  quadriurate.  Since  the  acidity 
of  wines  is  due  to  organic  acids  (mainly  tartaric,  malic, 
and  succinic  acids),  it  would  seem  very  doubtful,  judging 
from  the  results  of  these  experiments,  whether,  even  if 
any  alteration  in  the  alkalinity  of  the  blood  were  pro- 
duced by  the  drinking  of  acid  wines,  the  solubility  of  uric 
acid  in  such  blood  could  be  affected  in  the  slightest 
degree. 

Experiments  to  show  the  solvency  of  sodium  hiurate 
in  blood  serum  the  alkalinity  of  which  has  been  reduced 
by  the  addition  of  an  acid.' — The  effect  of  hydrochloric 
and  tartaric  acids  respectively  was  investigated.  The 
experiments  were  carried  out  in  a  similar  manner  to 
those  just  described,  except  that  an  excess  of  sodium 
biurate  was  substituted  for  the  uric  acid,  and  the 
digestion  with  the  sodium  biurate  was  carried  on  at 
100°  F.  for  five  hours.  The  following  tables  show  the 
results  :— 


78 


GOUT:    PATHOLOGY. 


[Part  I; 


TABLE    VII. 

Shoiving  the  sohthility  of  sodium  biurate  at  loo^  F.  in  unaltered  blood 
serum,  and  in  blood  serum  the  alkalinity  of  ivhich  is  proportion- 
ately reduced  by  the  addition  of  hydrochloric  acid. 


Solvent. 


Unaltered  serum 

Serum  one-fourth  neutralised  by  hydrochloric 
acid 

Serum  one-half  neutralised  by   hydrochloric 
acid 

Serum   three-fourths   neutralised  by  hydro- 
chloric acid 


Sodium  biurate 
dissolved. 


0.05   per   1,000 


0.05 


0.07 


These  results  show  that  sodium  biurate  is  sHghtly  more 

soluble  in  serum  which  has  been  partially  neutralised  by 

the  addition  of  hydrochloric  acid  than  it  is  in  unaltered 

serum. 

TABLE  VIII. 

Showing  the  solubility  of  sodium  biurate  at  100°  F.  in  unaltered  blood 
serum,  and  in  blood  serum  the  alkalinity  of  which  is  proportion- 
ately reduced  by  the  addition  of  tartaric  acid. 


Solvent. 


Unaltered  serum 

Serum  one-fourth  neutralised  by  tartaric  acid . 

Serum   one-half  neutralised   by  tartaric   acid 

Serum  three-fourths  neutralised  by  tartaric 
acid 


Sodium  biurate. 
dissolved. 


0.05  per   1,000 

0.08 

0.08 


These  results  also  show  that  sodium  biurate  is  more 
soluble  in  serum  the  alkalinity  of  which  has  been  reduced 


Chap.  IV.]  ALKALINITY    OF    BLOOD.  79 

by  the  addition  of  tartaric  acid  than  it  is  in  unaltered 
serum.  I  think  that  the  view  that  uric  acid  is  deposited 
in  the  Hver,  spleen,  joints,  and  fibrous  tissues  owing  to 
diminished  alkalinity  of  the  blood  should  be  abandoned. 
It  is  based  on  an  error — -viz.  that  the  deposit  is  uric  acid, 
whereas  it  is  sodium  biurate.  The  results  of  the  experi- 
ments that  have  just  been  described  indicate  that  diminu- 
tion of  the  alkalinity  of  the  medium  does  not  promote 
the  deposition  of  sodium  biurate.  The  other  view,  that 
increased  alkalinity  of  the  blood  dissolves  and  sweeps 
out  the  accumulations  of  uric  acid  from  the  various  organs 
and  tissues,  should  also,  in  my  opinion,  be  abandoned. 
It  is  based  on  the  same  error — ^viz.  that  the  deposit  is 
uric  acid,  whereas  it  is  sodium  biurate.  That  this  body 
is  not  more  soluble  in  highly  alkaline  fluids  has  been  proved 
by  the  experiments  of  Sir  William  Roberts,*  and  is  con- 
firmed by  the  experiments  that  have  just  been  described. 
Another  erroneous  idea  in  my  opinion  is  that  uric  acid 
may  be  precipitated  from  the  blood  in  the  form  of  in- 
soluble urates  by  certain  metallic  salts  ;  these  insoluble 
urates  are  supposed  to  be  deposited  in  various  tissues 
or  organs,  and  yet  in  some  mysterious  manner  to  be  sub- 
sequently redissolved  when  the  alkalinity  of  the  blood 
rises.  There  is  absolutely  no  experimental  proof  to  support 
such  a  statement. 

General  conclusions  drawn  from  the  investigations. — 
I.  The  alkalinity  of  the  blood  is  actually  increased 
during  a  gouty  attack. 

2.  The  solubility  of  uric  acid  in  the  blood  is  not  affected 
by  a  diminished  alkalinity  of  the  blood  produced  by  the 
addition  of  organic  acids. 

3.  The  deposition  of  sodium  biurate  is  not  accelerated 
by  a  diminution  of  the  alkalinity  of  the  blood. 

4.  An  increased  alkalinity  of  the  blood  does  not  in- 
crease the  solubility  of  deposits  of  sodium  biurate. 

*  Croonian  Lectures  on  "  Uric-Acid  Gravel  and  Gout,"  1892. 


8o  GOUT:    PATHOLOGY.  [part  i. 

Alkalinity  of  the  blood  and  precipitation  of  sodium 
biurate. — The  quadriurate  is,  in  the  dissolved  state,  a 
very  unstable  body,  and  soon  changes  into  the  sodium 
biurate,  which,  however,  is  not  at  once  pj-ecipitated,  since 
it  at  first  assumes  the  form  of  the  gelatinous  biurate,  in 
which  form  it  is  a  much  more  soluble  compound  than 
the  crystalline  biurate.  This  gelatinous  modification 
is  afterwards  converted,  either  slowly  or  rapidly, 
according  to  various  conditions,  into  the  crystalline  com- 
pound. 

The  results  will  now  be  given  of  some  experiments  con- 
ducted by  the  author  as  to  the  conditions  affecting  the 
conversion  of  the  gelatinous  into  the  crystalline  biurate ; 
they  apparently  promise  to  throw  some  light  on  the 
means  at  our  disposal  for  checking  a  gouty  attack  or  for 
diminishing  its  severity. 

Nature  of  the  experiments. — The  gelatinous  form  of 
sodium  biurate  is  about  five  times  as  soluble  in  blood 
serum  and  artificial  blood  serum  as  the  crystalline  variety, 
and  the  following  experiments  demonstrate  the  behaviour 
of  the  gelatinous  biurate  in  artificial  blood  serum.  The 
experiments  were  conducted  in  the  following  manner. 
Five  bottles  containing  artificial  blood  serum  at  98°  F., 
with  1.50  per  cent,  of  the  gelatinous  sodium  biurate  added, 
were  treated  thus  : — No.  i  was  left  unaltered,  No.  2 
had  its  alkalinity  increased  by  the  addition  of  o.i  per 
cent,  of  sodium  bicarbonate.  No.  3  by  the  addition  of 
0.3  per  cent.,  No.  4  by  the  addition  of  0.8  per  cent., 
and  No.  5  by  the  addition  of  i.o  per  cent.  The 
bottles  were  kept  in  a  warm  chamber  at  the  blood 
heat,  and  every  minute  a  small  quantity  of  the  con- 
tents of  each  bottle  was  removed,  examined  under  the 
microscope,  and  the  time  at  which  the  acicular 
crystals  of  sodium  biurate  first  made  their  appearance 
was  noted.  The  results  are  shown  in  the  following 
table  : — 


Chap.  IV.] 


SODIUM    BIURATE. 


8i 


TABLE    IX. 

Showing  the  time  effect  of  sodium  bicarbonate  on  the  conversion  of 
the  gelatinous  biurate  into  the  crystalline  form. 


Crystals  of  sodium 
biurate  first  ap- 
peared in. 


No.    I. — Artificial     blood     serum     containing 

1.50  per  cent,  of  gelatinous  sodium  biurate 
No.  2. — The  same  as  No.    i,  but  containing 

0.1  per  cent,  of  added  sodium  bicarbonate 
No.  3. — The  same  as  No.   i,  but  'containing 

0.3  per  cent,  of  added  sodium  bicarbonate 
No.  4. — The  same  as  No.    i,  but  containing 

0.8  per  cent,  of  added  sodium  bicarbonate 
No.   5. — The  same  as  No.   i,  but  containing 

i.o  per  cent,  of  added  sodium  bicarbonate 


10  minutes. 
7 
5 
3 
2 


These  results  show  that  the  proportionately  increased 
alkalinity  of  the  serum  with  sodium  bicarbonate  propor- 
tionately accelerated  the  conversion  of  the  gelatinous 
biurate  into  the  crystalline  variety.  It  was  also  very 
evident  to  the  naked  eye  at  the  end  of  half  an  hour  that 
the  higher  the  proportion  of  sodium  bicarbonate  present 
the  greater  was  the  bulk  of  the  precipitate.  The  five 
bottles  were  kept  in  the  warm  chamber  for  twenty-four 
hours,  when  their  contents  were  filtered,  and  the  respective 
amounts  of  sodium  biurate  remaining  in  solution  in  the 
gelatinous   form   were   estimated.     These   results   were    as 

follows  : — 

TABLE    X. 

Showing  the  effect  of  sodium  bicarbonate  on  the  conversion  of  the 
gelatinous  biiirate  into  the  crystalline  form  at  the  end  of  twenty- 
four  hours. 


No.  I 
No.  2 
No.  3 
No.  4 
No.   5 


Gelatinous  biurate 
left  in  solution  (in 
parts  per  1,000). 


0.64 
0.57 

0.43 
0.24 
0.22 


82 


GOUT:    PATHOLOGY. 


[Part  I. 


These  results  confirm  those  of  Table  IX.,  and  show  that 
the  higher  the  alkalinity  of  the  serum  from  the  presence 
of  sodium  bicarbonate  the  more  complete  is  the  con- 
version of  the  gelatinous  biurate  into  the  crystalline  variety, 
and  therefore  the  less  is  the  amount  of  the  gelatinous 
biurate  left  in  solution. 

A  precisely  similar  series  of  experiments  was  then 
conducted,  with  the  substitution  of  potassium  bicarbonate 
for  the  added  proportions  of  sodium  bicarbonate.  The 
results  are  set  out  in  : — 

TABLE    XI. 

Showing  the  time  effect  of  potassium  bicarbonate  on  the  conversion  of 
the  gelatinous  biurate  into  the  crystalline  form. 


Crystals  of  sodium 
biurate  first  ap- 
peared in 


No.  I. — Artificial  blood  semm  containing 
1.50  per  cent,  of  gelatinous  sodium  biurate 

No.  2. — The  same  as  No.  i,  but  containing 
0.1  per  cent,  of  added  potassium  bicarbon- 
ate          

No.  3. — The  same  as  No.  i,  but  containing 
0.3  per  cent,  of  added  potassium  bicar- 
bonate         

No.  4. — The  same  as  No.  i,  but  containing 
0.8  per  cent,  of  added  potassium  bicar- 
bonate         

No.  5. — The  same  as  No.  i,  but  containing 
i.o  per  cent,  of  added  potassium  bicar- 
bonate         


ID  mmutes. 


17 


35 


^,8 


The  results  show  that  the  presence,  of  potassium 
bicarbonate  in  the  serum  delays  the  precipitation  of  the 
crystalHne  biurate,  the  extent  of  the  delay  being  proportion- 
ate to  the  amount  of  potassium  bicarbonate  present.  It 
was  very  evident  to  the  naked  eye  at  the  end  of  an  hour 


Chap.  IV.] 


SODIUM    BIURATE. 


that  the  greater  the  proportion  of  potassium  bicarbonate 
present  the  smaller  was  the  amount  of  sodium  biurate 
precipitated.  The  effect  of  potassium  bicarbonate  on 
the  gelatinous  biurate  is,  therefore,  precisely  the  opposite 
of  that  of  sodium  bicarbonate. 

The  five  bottles  were  kept  in  the  warm  chamber  for 
twenty-four  hours,  when  their  contents  were  filtered, 
and  the  respective  amounts  of  sodium  biurate  remaining 
in  solution  in  the  gelatinous  form  were  estimated,  with  the 
following  results  :• — 

TABLE    XIT. 

Showing  the  effect  of  -potassium  bicarbonate  on  the  conversion  of  the 
gelatinous  biurate  into  the  crystalline  form  at  the  end  of  twenty- 
four  hours. 


Gelatinous      biurate 

left  in  solution  (in 

parts  per  i,ooo). 

No.   I 

0.62 

No.    2 

0.69 

No.   3 

0.78 

No.  4 

1 .01 

No.  5 

1 .09 

These  results  confirm  those  of  the  previous  table,  and 
show  that  the  greater  the  proportion  of  potassium  bicar- 
bonate present  in  the  serum  the  greater  is  the  inhibitory 
effect  on  the  conversion  of  the  gelatinous  biurate  into 
the  crystalline  form,  and  therefore  the  greater  is  the  amount 
of  the  gelatinous  biurate  left  in  solution. 

As  the  result  of  these  experiments  it  may  be  contended 
that  the  higher  the  alkalinity  of  the  blood  from  the  pre- 
sence of  sodium  bicarbonate,  the  more  rapid  and  the  more 
complete  is  the  conversion  of  the  soluble  gelatinous  biurate 
into  the  comparatively  insoluble  and  crystalline  form. 
In  connection  with  this  point  it  is  instructive  to  bear  in 
mind  that  mineral  waters  rich  in  sodium  bicarbonate  are 


84  GOUT:    PATHOLOGY.  [part  l 

well  known  to  accelerate  an  attack  of  gout  in  many  gouty 
subjects  ;  and  it  is  also  of  interest  again  to  mention  here 
that,  from  many  observations  made  on  the  alkalinity  of 
the  blood,  it  is  invariably  found  in  every  gouty  patient 
that  the  alkalinity  of  the  blood  is  higher  than  the  average 
alkalinity  of  the  blood  of  healthy  individuals. 

Since  this  increased  alkalinity  is  due  to  a  higher  pro- 
portion of  sodium  carbonate  or  bicarbonate,  it  can  be  under- 
stood why  such  blood  is  prone  to  hasten  and  to  augment 
the  formation  of  gouty  deposits.  On  the  other  hand,  it 
is  seen  that  when  the  increased  alkalinity  of  blood  serum 
is  due  to  the  presence  of  potassium  bicarbonate,  the  con- 
version of  the  gelatinous  biurate  into  the  crystalline  variety 
is  delayed  as  regards,  time,  and  is  considerably  diminished 
as  regards  quantity,  thus  explaining  the  well-known  bene- 
ficial effect  of  the  alkaline  potassium  salts  in  the  treat- 
ment of  acute  and  subacute  gout.  Von  Loghem  has  also 
shown  experimentally  that  increased  alkalinity  of  the 
tissue  fluids  leads  to  deposition  of  the  biurate,  while  dimin- 
ished alkalinity  lessens  the  tendency  to    uratic    deposits. 


CHAPTER   V. 
THE   GOUTY   DEPOSIT. 

Formation  of  the  gouty  deposit — Conditions  influencing  the  de- 
position of  sodium  biurate — Determining  cause  of  the 
gouty  deposit — The  lymph  circulation — Seats  of  uratic 
deposits  in  gout — Anatomical  seat  of  the  deposit  in  car- 
tilages. 

Formation  of  the  grouty  deposit.— Sir  William  Roberts 
investigated  the  behaviour  of  free  uric  acid  with  blood 
serum  and  kindred  media,  with  the  object  of  endeavouring 
to  throw  light  on  the  mode  in  which  sodium  biurate  origin- 
ates in  the  body,  and  on  the  conditions  which  control  the 
precipitation  of  sodium  biurate  in  the  gouty  system.  He 
experimented  with  solutions  of  uric  acid  in  blood  serum 
and  in  a  standard  solvent  which  was  prepared  as  follows  : — 

Composition  of  Roberts's  standard  solvent. 

Sodium  chloride  .  .  .  .0.5  gramme. 

Sodium  bicarbonate  .  .  .  .0.2  gramme. 

^_     Distilled  water  .  .  .  .    100  c.c. 

This  solution  represents  the  blood  serum,  in  so  far  as 
its  saline  ingredients  are  concerned.  Sir  William  Roberts 
found  that  it  reacted  with  uric  acid  and  the  urates  in  the 
same  manner  as  blood  serum  itself,  and  in  the  same  manner 
as  a  solution  comprising  all  the  salts  of  the  serum  in  their 
proper  proportions.  He  found  that  blood  serum  and 
the  standard  at  the  temperature  of  the  human  body  both 
dissolved  uric  acid  to  the  extent  of  about  one  part  in  500, 
thus  exhibiting  about  twenty  times  the  solvent  power 
that   the   same  media   exercise   on   sodium   biurate.     The 

85^ 


86  GOUT:    PATHOLOGY.  [part  i. 

chemical  and  solvent  power  is  dependent  on  the  sodium 
carbonate  contained  in  them,  and  is  due  to  that  body 
converting  the  uric  acid  into  sodium  quadriurate.  This 
sodium  quadriurate  which  remains  in  solution  is  gradually 
converted  by  the  excess  of  sodium  carbonate  into  sodium 
biurate,  and  this,  on  account  of  its  lesser  solubility,  is 
eventually  precipitated  in  the  crystalline  form.  Sir  William 
Roberts  inferred  from  these  results  that,  in  the  normal 
state,  uric  acid  is  primarily  taken  up  in  the  system  as 
quadriurate,  and  that,  as  such,  it  circulates  in  the  blood. 
The  detained  quadriurate,  circulating  in  a  medium  rich 
in  sodium  carbonate,  is  gradually  transformed  by  the 
latter  into  sodium  biurate,  which  is  less  soluble  and  is 
probably  less  easily  excreted  by  the  kidneys  than  the 
quadriurate.  This  biurate  is  probably  not  precipitated 
at  once,  since  it  would  most  probably  pass  at  first  into 
the  hydrated  or  gelatinous  condition,  which  is  a  much 
more  soluble  modification  of  sodium  biurate  than  the  crys- 
talline form  ;  but  with  due  lapse  of  time,  and  increasing 
accumulation,  it  passes  into  the  anhydrous  or  crystalline 
condition,  and,  as  this  form  is  almost  insoluble,  precipita- 
tion of  it  occurs,  or  is  likely  to  occur. 

The  reason  that  in  leuksemia  and  other  blood  diseases 
no  uratic  deposits  occur  is  that  the  uric  acid  produced  in 
the  various  organs  or  tissues  is  discharged  into  the  blood 
as  a  quadriurate,  and,  as  this  requires  some  hours  for  its 
maturation  before  it  is  possible  for  it  to  deposit  sodium 
biurate,  there  is  abundant  time  for  the  kidneys  to  eliminate 
it,  provided  these  organs  are  sound. 

Time  occupied  in  the  conversion  of  the  quadriurate 
into  the  biurate.' — The  period  of  time  required  for  the 
conversion  of  the  sodium  quadriurate  contained  in  the 
blood  into  the  biurate  is  variable,  and  is  doubtless  de- 
pendent on  several  factors,  such  as  the  amount  of  quadri- 
urate present,  and  the  proportions  of  various  saline  con- 
•^tituents  of  the  blood,  which  may  either  hasten  or  inhibit 


Chap,  v.]  THE    GOUTY    DEPOSIT.  87 

the  change.  This  last-mentioned  group  of  factors  is  a 
most  important  one  in  connection  with  the  therapeutical 
treatment  of  gout.  From  an  experimental  inquiry  into 
the  subject  that  I  have  made,  I  hnd  that  when  the  blood 
serum  is  saturated  with  sodium  quadriurate  and  kept  at 
the  body  temperature,  deposition  of  sodium  biurate  does 
not  commence  till  the  end  of  two  hours,  and  is  not  com- 
plete till  many  hours — sometimes  days — have  elapsed. 
Probably  in  no  pathological  condition  is  there  so  much 
sodium  quadriurate  present  in  the  blood  as  to  produce 
saturation.  The  smaller  the  proportion  of  quadriurate 
present,  the  longer  is  the  deposition  of  sodium  biurate 
delayed,  and  the  longer  is  the  time  required  to  complete 
its  precipitation. 

Deposition  of  sodium  biurate  encouragred  by  con- 
centration of  medium  and  proportions  of  sodium  salts 
present. — Sir  William  Roberts  found  that  sodium  biurate 
is  very  sparingly  soluble  in  blood  serum  ;  at  blood  heat 
the  amount  dissolved  is  about  one  part  in  10,000  (about 
one-tenth  of  its  solubility  in  water).  This  lessened  solu- 
bility is  entirely  due  to  the  saline  ingredients  of  the  serum, 
as  on  depriving  the  serum  of  its  salts  by  dialysis,  it  was 
then  found  to  exercise  the  same  solvent  action  on  the 
biurate  as  simple  water.  Sir  William  Roberts  found  that 
the  sodium  salts  especially  diminish  the  solvent  power 
of  a  medium  for  sodium  biurate,  and  that  this  diminished 
power  is  mainly,  if  not  entirely,  due  to  the  sodium,  and 
is  apparently  not  much,  if  at  all,  influenced  by  the  acids 
combined  with  it,  since  solutions  of  sodium  bicarbonate, 
chloride,  sulphate,  phosphate,  and  salicylate,  prepared 
so  that  the  percentage  of  sodium  in  them  was  the  same, 
exhibited  the  same  low  solvent  action.  His  experiments 
also  show  that  if  a  medium  be  rich  in  urates,  but  poor  in 
sodium  salts,  its  tendency  to  precipitation  is  feeble,  and 
vice  versa.  Since  structures  belonging  to  the  connective- 
tissue  class  are  rich  in  sodium  salts  and  are  also  liable  to 


S8  ,  GOUT:    PATHOLOGY.  [Part  l 

uratic  deposits,  while  muscle,  brain,  liver,  and  spleen 
are  poor  in  sodium  salts  and  not  liable  to  uratic  deposits, 
he  considers  that  the  proportion  of  sodium  salts  in  a  tissue 
is  an  important  factor  in  determining  the  deposition  of 
urates  in  that  issue. 

Precipitation  of  sodium  biurate  from  synovial 
fluid.- — Another  factor  in  facilitating  the  precipitation  of 
urates  is  to  be  found  in  the  synovial  fluid.  Sir  William 
Roberts's  view  is  that  the  uratic  precipitation  actually 
takes  place  from  the  synovial  fluid,  and  does  not  origin- 
ate in  the  cartilaginous  substance.  This  view  is  based 
in  part  on  the  microscopic  appearance  of  vertical  sections 
of  gouty  cartilage,  in  which  the  deposit  is  seen  to  be  great- 
est on  the  synovial  surface  of  the  cartilage  and  to  become 
gradually  sparser  and  sparser  towards  the  deeper  layers, 
and  in  part  on  the  fact  that  synovial  fluid  has  been  re- 
peatedly found  heavily  laden  with  crystals  of  sodium 
biurate.  He  considers  (as  opposed  to  Ebstein's  view) 
that  the  process  of  deposition  in  the  cartilage  is  a  purely 
passive  and  physical  one,  and  that  the  synovial  fluid,  charged 
with  its  dissolved  urate,  penetrates  by  liquid  diffusion 
into  the  superficial  layers  of  the  cartilage,  and  that,  when 
the  critical  moment  arrives,  precipitation  takes  place 
simultaneously  in  the  synovia  and  in  the  cartilage.  Accord- 
ing to  this  view,  the  after-consequences  are  entirely  second- 
ary, and  are  due  to  inflammation  set  up  by  the  presence 
of  the  foreign  body  in  the  tissue. 

As  regards  the  varying  liability  of  different  joints  to 
gouty  attacks.  Sir  \yilliam  Roberts  considers  that  it  is, 
at  all  events  in  part,  dependent  on  a  greater  concentration 
of  the  synovia  of  some  joints,  and  on  a  variable  proportion 
of  sodium  salts  and  possibly  of  sodium  biurate.  The  ex- 
periments made  by  Frerichs  *  on  the  comparative  com- 
position of  the  synovia  of  animals  leading  idle  and. active 
existences   somewhat   support   this   view.     Frerichs   found 

*  R.  Wagner's  '  Handworterbuch  der  Physiologic,"  1884,  Bd.  iii.,  Part  i. 


Chap,  v]  THE    GOUTY    DEPOSIT.  89 

that  the  synovia  of  stall-fed  horses  and  oxen  leading  an 
idle  existence  was  more  watery  and  contained  a  larger 
proportion  of  sodium  salts  than  the  synovia  of  similar 
animals  doing  work  or  roaming  in  the  meadows.  More- 
over, the  joints  of  the  idle  animals  contained  twice  as  much 
synovia  as  the  joints  of  similar  animals  taking  active 
exercise. 

Deposition  of  sodium  biurate  encourag-ed  by  slug- 
gish  movement  of  medium. —  It  is  highly  probable  that 
the  very  sluggish  movement  of  fluids  in  the  cartilaginous 
and  fibrous  tissues  favours  the  deposition  of  urates  from 
the  medium  in  which  they  are  dissolved.  As  illustrating 
the  fact  that  whatever  interferes  with  the  movement  of 
the  animal  fluids  favours  the  production  of  gouty  symp- 
toms, or  of  an  actual  attack  of  gout,  an  interesting  case 
has  been  recorded  by  Charcot,  who  observed,  in  a  hemi- 
plegic  woman  of  forty,  that  most  of  the  articular  carti- 
lages on  the  right,  paralysed,  side  were  infiltrated  with 
urates,  whereas  those  of  the  non-paralysed  side  showed 
no  such  deposits.  Sir  William  Roberts  considers  that 
the  chief  reason  why,  in  the  post-mortem  room,  the  car- 
tilages figure  more  prominently  than  the  fibrous  structures 
as  the  seat  of  deposition  of  sodium  biurate  is  to  be  found 
in  the  fact  that  in  the  fibrous  tissues  there  is  a  comparatively 
free  lymph  flow,  which  exercises  a  more  effective  solvent 
action  on  uratic  deposits  than  can  be  effected  by  the  slug- 
gish lymph  flow  in  the  cartilages.  With  regard  to  the 
reason  or  reasons  that  gouty  precipitation  takes  place 
preferentially  in  synovia  rather  than  in  the  serum  of  blood 
and  lymph,  Sir  W.  Roberts  considers  that  the  motionless 
condition  of  synovia  as  compared  with  the  state  of  rapid 
movement  of  blood  and  lymph  would  give  to  synovia 
a  priority  in  uratic  precipitation. 

Deposition  of  sodium  biurate  encourag-ed  by  injury 
to  joints  or  by  interference  with  their  nutrition. 
-^A  slight  injury  to  a  joint,  which  in  a  healthy  person 


go  GOUT :    PATHOLOGY. "  [Part  i. 

would  speedily  pass  off,  in  a  gouty  person  renders  the 
part  susceptible  to  the  deposition  of  sodium  biurate  if 
sodium  quadriurate  be  circulating  in  the  blood.  This 
susceptibility  is  probably  in  some  way  connected  with  an 
impairment  of  the  nutrition  of  the  affected  tissues.  Fagge, 
indeed,  regarded  a  paroxsymal  attack  of  gout  in  the  light 
of  an  accident  occurring  in  the  course  of  an  essentially 
chronic  change  in  the  joint  affected. 

As  regards  the  relation  between  gout  and  rheumatism, 
Sir  Alfred  Garrod  has  remarked  that  if  gout  supervene 
in  individuals  who  have  suffered  from  rheumatism,  it  is 
generall}^  the  articulations  which  were  the  seat  of  rheu- 
matism that  are  first  attacked  by  gout.  So  that  joints 
which  have  been  the  seat  of  acute  rheumatism  are  especially 
predisposed,  in  gouty  subjects,  to  become  the  seat  of  uratic 
deposits. 

Ebstein  *  considers  that  deposition  of  sodium  biurate 
is  dependent  on  and  is  produced  by  previous  necrosis 
of  the  affected  tissues,  and  that  the  uratic  deposit  never 
occurs  in  a  normal  tissue.  His  view  is  that  the  neutral 
sodium  urate  circulating  in  the  blood  acts  as  an  irritant 
and  produces  necrosis  of  the  cartilages  or  other  tissues, 
in  which  the  sodium  biurate  is  subsequently  deposited  ; 
as  a  result  of  this  necrosis  he  considers  that  an  acid  is 
developed  which  converts  the  neutral  urate  into  acid 
urate,  which  compound  is  then  deposited  in  the  necrosed 
areas.  This  theory  is  obviously  an  erroneous  one,  since 
the  neutral  sodium  urate  cannot  exist  in  the  circulation. 
Klemperer  f  does  not  consider  that  uric  acid  is  responsible 
for  the  necrotic  changes  in  tissues,  nor  that  the  phenomena 
of  gout  can  be  due  to  mere  crystallisation  of  sodium  biurate 
from  the  blood,  because  in  leukaemia,  where  an  excess 
of  urate  is  present  in  the  blood,  neither  local  necrosis 
nor  uratic  deposits  occur.     He  believes  that  some  unknown 

*  "  Die  Natur  und  Behandlung  der  Gicht,"  1882. 
t  Deut.  medicin.  Woch.,  1895,  vol.  xxi.,  p.  655. 


Chap.  V.]  SEATS    OF    GOUTY    DEPOSITS.  91 

substances,  in  gout,  lead  to  inflammatory  and  necrotic 
processes  in  various  tissues  ;  these  necrotic  areas  then 
attract  the  uric  acid  from  the  blood,  the  chemical  affinity 
of  the  necrotic  parts  for  uric  acid  being  so  great  that  the 
blood  cannot  redissolve  it.  Von  Noorden  thinks  the  un- 
known substance  which  starts  the  inflammatory  and 
necrotic  processes  is  a  ferment,  and  that  the  uric  acid 
crystallises  out  in  the  necrotic  tissues. 

Reasons  for  the  special  selection  of  the  great 
toe  and  ear  as  seats  of  grouty  deposits.— There  are 
several  reasons  to  account  for  the  special  causation  of 
uratic  deposits  in  the  great  toe.  (i)  Tliere  is  the  liability 
of  the  metatarso-phalangeal  joint  to  injury  from  having 
to  support  the  weight  of  the  body,  and  from  being  sub- 
jected to  sudden  shocks.  (2)  The  remoteness  of  the  joint 
from  the  heart,  and  the  force  of  the  circulation  being 
consequently  at  its  minimum  at  that  part.  (3)  The  poor 
vascularity  of  the  tissues  of  the  joint.  The  liability  of 
the  joint  to  injury  is  shown  by  Garrod's  examinations  of 
the  great-toe  joints  of  twenty  subjects  known  not  to  have 
had  gout.  In  fourteen  he  found  ulceration  of  the  cartilages 
of  one  or  both  joints.  Of  these  twenty  subjects  three 
were  under  thirty  years  of  age  and  showed  no  ulceration 
of  the  cartilages  ;  the  remaining  seventeen  were  over 
thirty  years  of  age,  and  of  these  fourteen,  or  82  per  cent., 
showed  ulceration  of  the  cartilages.  All  the  subjects 
over  fifty  years  of  age  showed  ulceration. 

In  the  helix  of  the  ear  the  sluggish  circulation  and 
the  coldness  of  the  organ  are  quite  sufficient  to  account 
for  the  frequency  with  which  uratic  deposits  are  found 
in  that  part. 

While  the  usual  course  of  the  disease  is  for  the  great- 
toe  joint  to  be  the  part  first  affected,  in  not  a  few  cases 
the  primary  attack  occurs  in  the  knees,  ankles,  tarsus,  or 
hands.  The  actual  site  of  the  attack  is  frequently  deter- 
mined by  some  previous  injury  to  the  part  affected,  by 


92  GOUT:    PATHOLOGY.  [Part  l 

which  its  vitaHty  has  been  weakened,  and  the  part  rendered 
more  prone  to  the  attack  of  the  toxins.  When  the  swelhng 
increases  the  pain  lessens  ;  later  the  parts  pit  on  pressure, 
and  the  cuticle  cracks  and  desquamates. 

Determining"  cause  of  the  grouty  deposit. — The  whole 
series  of  periarthritic  and  arthritic  changes  in  gout  are 
in  all  probability  the  result  of  slow  chronic  intoxication, 
with  local  necrosis,  at  points  of  least  vitality.  The  intoxica- 
tion and  the  local  necrosis  are  probably  due  to  the  action 
of  a  bacterial  toxin  or  toxins. 

The  tissue  lymph  or  lymph  circulation  in  the 
areolar  tissue. — This  subject  is  one  that  has  an  intimate 
bearing  on  the  production  of  the  cedema  and  the  forma- 
tion of  the  gouty  deposits  in  various  forms  of  gout. 

G.  Oliver,*  in  the  course  of  experiments  on  blood, 
found  that  the  rolling  of  a  tight  rubber  ring  over  the  finger 
from  the  tip  to  beyond  the  interphalangeal  joints  as  a 
rule  considerably  raises  the  percentage  of  the  blood  cor- 
puscles, and  of  the  haemoglobin.  From  the  observation 
of  this  fact  he  was  forced  to  the  conclusion  that  the  ring 
not  merely  emptied  the  vessels,  but  likewise  cleared  away 
any  tissue  fluid  present  in  the  skin  and  subcutaneous 
tissues. 

The  needle,  in  puncturing  the  capillaries,  liberates  a 
certain  portion  of  lymph  from  the  areolar  tissue  which 
surrounds  them,  and  this  dilutes  the  blood.  When,  how- 
ever, both  fluids  have  been  dispersed  by  the  compression 
of  the  rubber  ring  a  puncture  made  just  before  the  removal 
of  the  ring  yields  blood  from  the  vessels  only  ;  for  the  blood 
instantly  returns  to  the  vessels,  whereas  an  appreciable 
interval  must  elapse  before  the  lymph  reappears  or  is 
exuded  afresh. 

Oliver's  method  of  observation  is  first  to  take  a  sample 
of  blood  from  the  first  easily  flowing  drop  derived  from 
a  puncture  at  the  root  of  the  nail,  the  object  being  to  obtain 

*■  Lancet,  1903. 


CHAP.  V.J  TISSUE    LYMPH.  93 

the  actual  proportion  of  lymph  present  in  the  tissues 
around  the  puncture.  Three  stout  rubber  rings  are 
then  rolled  in  succession  from  the  tip  of  the  finger 
to  beyond  the  interphalangeal  joints,  and  these  are 
then  removed  by  placing  over  the  finger  a  rigid  tube, 
on  to  which  the  rings  are  rolled  ;  in  this  way  com- 
pression of  the  tissues  is  secured  in  one  direction  only 
— namely,  from  the  tip.  The  original  puncture  will 
generally  suffice  for  supplying  the  second  sample.  The 
finger  is  held  upwards  until  the  blood  is  made  to  flow, 
for  observation  shows  that  compression  does  not  now 
alter  the  proportion  of  the  corpuscles.  The  hsemocyto- 
meter  tubes  are  then  read  in  the  usual  way,  and  the  differ- 
ence between  the  readings  indicates  the  percentage  of 
tissue  lymph.  The  following  are  some  of  Oliver's  general 
conclusions  : — 

1.  The  ingestion  of  food  produces  a  rapid  flow  of  lymph 
into  the  tissue  spaces,  which  in  an  hour  after  meals  attains 
its  maximum  development,  and  then  slowly  subsides  and 
only  ceases  after  the  lapse  of  from  three  to  four  hours. 

2.  The  interchange  of  fluid  between  the  blood  and 
the  tissues  may  be  measured,  and,  as  showing  the  large 
amount  of  lymph  that  flows  from  the  blood  into  the  areolar 
tissues,  Oliver  calculates  that  a  man  weighing  eleven  stones 
should  exude  twenty-eight  fluid  ounces  of  lymph  into  the 
interstitial  spaces  of  his  tissues  after  each  meal.  This 
large  interchange  of  fluid  between  the  blood  and  the  body- 
tissues  excites  other  fluid  transfers  from  the  blood;  con- 
sequently when  the  maximum  exudation  takes  place  the 
volume  of  the  blood  will  shrink  considerably.  During 
absorption  it  will  increase,  and  when  absorption  is  com- 
pleted it  will  acquire  its  fullest  expansion. 

3.  Exudation  of  tissue  lymph. — Physiologists  are  divided 
as  to  whether  tissue  lymph  is  a  pressure  product  or  a  secre- 
tion. Oliver,  as  well  as  Ludwig,  Starling  and  others,  con- 
siders it  to  be  a  pressure  product,  inasmuch  as  the  amount 


94  GOUT :    PATHOLOGY.  [Part  i. 

of  lymph  in  normal  subjects  is  always  proportionate  to 
the  rise  in  the  blood  pressure. 

4.  Absorption  or  disposal  of  tissue  lymph. — In  the 
normal  condition  of  circulation  each  exudation  of  lymph 
completely  disappears  before  its  successor  is  drawn  out. 
Lymph  can  only  be  disposed  of  in  two  ways  : — (i)  by 
absorption  into  the  capillaries,  and  (2)  by  transmission 
along  the  lymphatics.  When  the  body  is  in  a  state  of 
rest,  the  fluid  exuded  into  the  tissues  is  mainly  absorbed 
directly  into  the  blood,  and  an  essential  condition  re- 
quired to  effect  this  absorption  is  a  falling  capillary  pres- 
sure. Should  the  blood  pressure  remain  high,  absorption 
ceases  to  go  on  and  the  lymph  flow  from  the  tissues  is 
arrested,  as  well  as  the  continuous  discharge  of  lymph  in  the 
tissues  of  those  in  whom  the  blood  pressure  is  supernormal. 

5.  Intermediary  circulation. — The  to-and-fro  transfer- 
ance  of  fluid  from  the  capillary  to  the  tissue  spaces  con- 
stitutes a  circulation  which  appears  to  suffice  for  all  the 
requirements  of  metabolism  while  the  body  is  in  a  state 
of  rest.  This  circulation,  interposed  as  it  is  between  the 
capillaries  and  the  lymphatic  vessels,  is  termed  by  Oliver 
the  "  intermediary  circulation."  It  is  merely  an  extra- 
vascular  extension  of  the  capillary  circulation  controlled 
by  the  forces  which  actuate  that  circulation. 

6.  Physiological  ends  served  by  the  tissue  lymph  cir- 
culation.— Inasmuch  as  proteids  are  diffused  through 
membranes  in  proportion  to  the  pressure  brought  to  bear 
upon  them,  it  may  be  inferred  that  the  physiological  end 
served  by  the  rise  in  the  capillary  blood  pressure  which 
produces  the  digestive  exudations  of  lymph  is  to  supply 
pabulum  to  the  tissues.  Proteids  are  therefore  probably 
distributed  to  them  in  the  exudation  current  which  flows 
from  the  blood.  Inasmuch  as  absorption  does  not  com- 
mence until  the  blood  pressure  begins  to  fall,  the  current 
from  the  tissue  spaces  to  the  capillaries  will  not  set  in 
until  after  the  acme  of  the  wave  has  been  reached.     This 


Chap,  v.]  TISSUE    LYMPH.  95 

return  stream  probably  consists  of  a  solution  of  salts  and 
waste  products  only,  and  any  surplus  of  proteids  not  used 
up  in  construction  and  repair  of  the  tissues  may  be  restored 
to  the  blood  by  transmission  along  the  lymphatics  rather 
than  by  direct  retransfer  through  the  capillary  wall,  for 
there  is  a  difficulty  in  explaining  how  proteids  can  be 
absorbed  from  the  tissues  by  this  direct  route.  If  these 
views  on  the  physiological  purport  of  the  lymph  waves 
be  correct  it  maybe  inferred: — (i)  That  the  intermediary 
circulation  provides  the  mechanism,  as  it  were,  for  the 
supply  of  pabulum  to  the  tissues  and  for  the  removal 
of  soluble  waste  products  from  them.  (2)  That  the 
lymph  wave  which  follows  a  meal  insures  the  immediate 
supply  of  pabulum  from  the  blood  which  restores  all  the 
tissues  of  the  body  at  once  and  long  before  the  food  itself 
can  be  assimilated  into  the  blood.  Thus  it  is  that  the 
ingestion  of  food  secures  the  speedy  renewal  of  the  energies, 
which  is  a  matter  of  common  experience  ;  and  therefore 
the  exhausted  tissues  have  not  to  remain  unsupplied  with 
fresh  nourishment  until  the  food  taken  becomes  part  of 
the  common  store  of  pabulum  which  the  blood  keeps 
ready  for  distribution.  (3)  That  beverages  (tea,  coffee, 
and  alcohol)  probably  invigorate  the  body  by  inciting  a 
flow  of  lymph  into  the  tissues.  Beverages,  however,  viewed 
from  this  standpoint  differ  from  food-stuffs  in  that  they 
fail  to  restore  to  the  blood  the  outflow  of  pabulum  which 
they  create.  They  are  therefore  but  temporary  expedients 
of  nutrition. 

7.  When  the  blood  pressure  becomes  supernormal,  as 
in  high  altitudes,  in  chronic  goutiness,  and  in  kindred 
ailments,  the  density  of  the  blood  rises  in  proportion  to 
the  increased  and  persistent  exudation  of  tissue  lymph  ; 
and  when  the  pressure  falls  below  the  normal  range  the 
fluid  exchange  between  the  blood  and  the  tissues  diminishes, 
and  the  density  of  the  blood  tends  to  be  low,  and,  indeed, 
is  generally  low. 


96  GOUT:    PATHOLOGY.  [part  i. 

8.  In  all  the  cases  of  undoubted  gout  examined  by 
Oliver  an  obstructed  form  of  the  intermediary  circulation 
was  found,  but  whether  it  is  invariably  present  in  gout 
cannot  at  present  be  affirmed.  All  the  remedial  measures 
which  counteract  chronic  goutiness  liberate  the  embarrassed 
peripheral  circulation  by  reducing  the  increased  venular 
resistance,  and  thus  they  secure  a  rise  in  the  venous  pres- 
sure, a  fall  in  the  capillary  pressure,  and  a  reduction  in 
the  mediary  circulation  of  tissue  lymph.  When  the 
obstructed  intermediary  circulation  in  gouty  subjects  is 
thus  relieved  and  the  normal  flow  and  ebb  of  tissue  lymph 
are  restored,  the  general  health  is  improved  and  the  local 
manifestations  of  the  gouty  state,  as  a  rule,  either  dis- 
appear or  are  lessened. 

9.  Oliver  considers  that  his  experiments  afford  some 
confirmation  of  the  correctness  of  the  generally  entertained 
opinion  that  goutiness  primarily  depends  on  the  retention 
of  some  waste  product  or  products.  There  may  be  differ- 
ences of  opinion  as  to  how  gout  originates,  but  as  to  how 
it  is  maintained  when  established  he  considers  that  his 
observations  leave  no  doubt.  They  have  shown  that  it 
is  essentially  dependent  on  a  derangement  of  the  inter- 
mediary circulation,  and  that  therefore  the  tissues  them- 
selves form  the  arena  in  which  gouty  disturbances  develop 
and  manifest  themselves.  Residua  may  accumulate  and 
be  deposited  in  the  interstitial  spaces  of  the  tissues,  be- 
cause their  removal  is  thwarted,  either  by  an  excessive 
capillary  blood  pressure  limiting  the  absorption  of  fluid 
from  these  spaces,  or  by  a  diminution  of  that  pressure 
reducing  the  fluid  exchange  between  the  blood  and  the 
tissues.  Hence  the  two  leading  types  of  gout  which  are 
well  recognised.  According  to  his  observations,  the  con- 
tinuous presence  of  a  large  quantity  of  tissue  lymph  pro- 
vides an  important  condition  for  the  development  of  the 
local  manifestations  of  gout,  which  were  present  in  by 
far  the  majority  of  the  cases  observed,  and  those  few  cases 


Chap.  V.]  GOUTY     DEPOSITS.  97 

in  which  local  signs  of  gout  had  not  so  far  declared  them- 
selves might  fairly  be  said  to  be  gouty — in  the  sense  of 
potential  gout. 

Chalmers  Watson,  from  an  examination  of  gouty  de- 
posits in  tendons,  cartilages,  and  bone,  came  to  the  follow- 
ing conclusions  :■ — 

1.  The  examination  of  gouty  tendons  showed  that  the 
necrotic  areas  had  a  definite  relation  to  the  vessels  of  the 
part.  The  appearances  in  the  tendons  indicated  that  the 
necrotic  areas  are  to  be  accounted  for  by  an  infection  by 
the  blood  stream. 

2.  The  erosion  of  cartilage  was  due  not  to  the  presence 
of  uric  acid,  but  to  the  action  of  small  round  cells  of  the 
granulation  tissue  type. 

3.  In  connection  with  the  gouty  deposits  in  the  bone, 
there  were  noticed  a  richness  of  the  blood  supply,  the  pre- 
sence of  giant  cells,  and  great  accumulation  of  small  round 
cells  of  the  nature  commonly  associated  with  the  action 
of  bacterial  toxins. 

4.  The  general  conclusion  was  that  the  tout  ensemble 
of  the  pathological  pictures  is  strikingly  similar  to  that 
seen  in  chronic  infective  diseases.  From  this  point  of  view 
the  uric  acid  is  regarded  as  the  feature  which  gives  the 
inflammation  its  specific  character. 

Seats  of  uratic  deposits  in  grout. — Uratic  deposits 
are  found  almost  exclusively  in  structures  belonging  to 
the  connective-tissue  class — in  cartilages,  ligaments,  tendons, 
and  in  the  cutaneous  and  subcutaneous  connective  tissue. 
Although  the  uratic  deposits  are  seen  most  characteristically 
in  joint  structures,  yet  they  have  been  found  in  nearly  all 
the  structures  of  the  body  which  contain  a  large  amount 
of  connective  tissue.  In  the  central  nervous  system 
crystals  of  sodium  biurate  have  been  found  in  the  dura 
and  pia  mater,  in  the  neurilemma  of  nerve-sheaths,  in 
patches  of  cerebral  softening,  and  in  the  cerebro-spinal 
fluid.     A  similar  condition  has  been  noted  in  the  cardio- 


98  GOUT:    PATHOLOGY.  [part  i. 

vascular  system,  the  aortic  and  mitral  valves  and  aorta 
occasionally  showing  a  deposit.  Among  other  sites  may 
be  mentioned  the  eyelids,  sclerotic,  auricle,  tendons  and 
tendon  sheaths,  vocal  cords,  bronchi,  bursee,  bone  marrow, 
palmar  and  other  fascia,  and  subcutaneous  tissue  generally. 
Indeed,  it  is  probable  that  a  careful  examination  of  the 
various  organs  and  tissues  in  pronounced  cases  of  gout 
would  reveal  the  presence  of  a  deposit  in  many  other 
places  not  previously  described.  These  points  sufficiently 
indicate  that  uratic  precipitation  is  very  variable  in  its 
incidence' — a  fact  of  considerable  import  in  connection 
with  the  phenomena  of  irregular  gout. 

A  deposit  of  sodium  biurate  may  occur  in  an  enlarged, 
thickened,  and  inflamed  bursa,  in  which  case  the  swelling 
may  reach  a  considerable  size.  Tophi  vary  in  size  from 
a  very  minute  deposit,  the  size  of  a  pin's  head,  up  to  or 
exceeding  that  of  a  small  orange.  Among  the  more  common 
situations  are  the  ears,  fingers,  foot,  ankle,  and  eyelids, 
but  they  may  be  seen  in  other  situations.  The  general 
appearances  vary  according  to  the  site,  and  the  presence 
or  absence  of  ulceration. 

Although  tophi  originally  consist  of  sodium  biurate, 
yet,  if  they  persist  long  enough,  they  come  to  contain 
both  phosphate  and  carbonate  of  lime,  and  the  gouty 
nodosities  about  a  joint  may  ultimately  form  true  bone. 

Anatomical  seat  of  the  deposit  in  cartilages. — The 
uratic  deposit  first  occurs  in  the  central  portion  of  articular 
cartilage' — a  point  farthest  from  the  network  of  nutrient 
capillaries  and  a  point  whose  nutrition  is  more  easily  retarded. 
It  is  also  probably  the  point  of  greatest  pressure ;  hence 
a  long  walk,  a  dance,  or  similar  violent  exercise  may  pre- 
cipitate an  attack  of  gout.  Uratic  deposits  occur  in  car- 
tilages, ligaments,  synovial  membranes  and  their  fringe- 
like processes.  In  synovial  membranes  the  deposit  is 
not  on  the  surface,  but  in  the  subserous  tissue.      Ebstein* 

*  "  Die  Natur  und  Behandlung  der  Gicht,"   i88?, 


Chap,  v.]  GOUTY    DEPOSITS.  99 

states  that  directly  under  the  surface  of  the  cartilage  a 
very  shallow  tissue  layer  exists  in  which  crystals  are  want- 
ing, and  in  the  layer  immediately  beneath  this  the  crystals 
are  most  plentiful.  He  agrees  with  Sir  Alfred  Garrod 
that  only  two-thirds  of  the  thickness  of  the  cartilage  is 
usually  infiltrated,  although  exceptionally — as  shown  by 
Cornil  and  Ranvier — the  whole  cartilage  may  be  infiltrated. 
With  regard  to  the  exact  relation  of  the  uratic  deposit 
to  the  various  elements  of  articular  cartilage,  the  cartilage 
cells  are  held  to  be  the  centres  of  primary  deposit  by  Cornil 
and  Ranvier,  Charcot,  Rindfleisch,  Budd,  and  Garrod. 
Cornil  and  Ranvier  consider  that  nutritive  disturbances 
in  the  cartilage  cells  precede  the  deposition  of  sodium  urate. 
Rindfleisch  and  Budd,  however,  consider  that  the  carti- 
lage cells  do  not  take  any  active  part.  Some  observers, 
including  Sir  Dyce  Duckworth,  consider  that  the  deposition 
occurs  quite  indiscriminately,  not  selecting  for  its  original 
site  any  particular  element  of  the  cartilage.  Others,  as 
Bramson,  Rokitansky,  and  Auguste  Foerster,  think  that 
urates  deposit  in  the  intercellular  cartilaginous  substance. 
When  a  gouty  joint  is  examined  in  the  earlier  stages 
of  the  disease  the  articular  cartilages  show  scattered  or 
isolated  points,  streaks,  or  patches  of  a  chalk-like 
material — sodium  biurate.  A  closer  examination  may 
reveal  the  fact  that  this  deposit  is  not  really  on  the  surface 
of  the  cartilage,  but  is  situated  interstitially  in  its  sub- 
stance, the  superficial  layer  of  epithelium  being  intact. 
Later  this  superficial  layer  is  involved,  and  the  articular 
surface  becomes  roughened,  irregular,  and  eroded.  As 
the  primary  deposits  take  place  in  the  areas  where  circu- 
lation and  nutrition  are  at  their  lowest  level,  we  accord- 
ingly find  that  it  is  the  central  portion  of  the  articular 
cartilage  that  shows  the  earliest  manifestations.  Later 
on  the  ligamentous  structures  may  become  the  seat  of 
interstitial  deposit,  and  the  synovial  membranes  and  their 
fringe-like  processes  are  involved. 


100 


GOUT  :    PATHOLOGY.  [Part  i. 


The  ends  of  the  bones  occasionally  become  enlarged, 
and  even  true  bony  ankylosis  may  occur.  Changes  also 
take  place  outside  the  joints,  the  connective  tissues,  apon- 
euroses, and  tendon  sheaths  becoming  the  seat  of  a  varying 
amount  of  uratic  infiltration.  Inflammatory  changes  occur 
in  the  cartilage  leading  to  proliferation  and  necrosis,  the 
former  being  most  manifest  at  the  periphery  of  the  cartilage, 
where  the  deposits  are  smaller  and  the  tissues  more  highly 
vascularised.  As  a  result,  outgrowths  may  occur  at  the 
margin  of  the  articulation. 


PART  IL 

^ETIOLOGY    AND    VARIETIES    OF   GOUT- 
DIAGNOSIS    AND    PROGNOSIS. 

CHAPTER    VL 
/ETIOLOGY   AND   CLINICAL   FEATURES. 

Etiology  of  gout — Heredity — Immediate  exciting  cause — The 
clinical  features  of  acute  gout — The  clinical  features  of  chronic 
gout — The  kidneys  in  chronic  gout. 

^tiologry  of  grout. — Age. — Gout  is  mainly  a  disease  of 
middle  and  late  life,  but  it  may  occur  earlier  if  there  is 
a  marked  hereditary  tendency.  While  gout  is  commonly 
a  disease  of  adult  life,  not  appearing  as  a  rule  under  the 
age  of  thirty-five,  there  are  numerous  exceptions  to  this. 

Sex. — Gout  is  much  more  common  among  males.  This 
tendency  is  no  doubt  mainly  due  to  the  fact  that  the  habits 
of  men,  with  regard  to  diet  and  alcoholic  drinks,  are  more 
conducive  to  the  development  of  the  disease  than  the 
more  temperate  habits  of  life  of  the  majority  of  women. 

Geographical  distribution. — It  is  generally  conceded 
that  in  England  the  disease  is  more  prevalent  than  in 
any  other  country  in  the  world.  In  this  country  there 
has  for  many  generations  been  a  large  leisured  class  who 
have  been  over-indulgent  in  eating  and  drinking,  and  who 
at  the  same  time  have  taken  insufficient  exercise. 

There  has  been  a  general  impression  prevalent  both 
within  and  outside  the  United  vStates  that  gout  is  a  rare 
disease    in    that    country.      It   is,   however,   much   more 

lOI 


102       GOUT:    iETIOLOGY   AND   VARIETIES,  [part  11= 

prevalent  there  than  is  generally  supposed.  At  the  Johns 
Hopkins  Hospital,  Baltimore,  out  of  the  total  medical 
cases  admitted  to  the  wards  during  fourteen  years  0'26 
per  cent,  were  cases  of  gout.  For  a  similar  period  at 
St.  Bartholomew's  Hospital,  out  of  the  total  medical  cases 
admitted  to  the  wards,  0*37  per  cent,  were  cases  of  gout. 
So  that  in  London,  the  home  of  gout,  the  cases  are  a  little 
less  than  one-third  more  frequent  than  they  are  at  Balti- 
more. The  disparity  is,  therefore,  not  at  all  marked,  and 
is  probably  even  less  than  that  shown  by  these  figures, 
since  it  has  been  generally  conceded  in  the  past  by  medical 
men  in  America  that  gout  is  not  as  a  rule  so  thoroughly 
diagnosed  as  in  this  country,  and  that  many  cases  of  true 
gout  are  mistaken  for  rheumatism. 

Hereditary  predisposition. — As  regards  the  oft-debated 
question  of  heredity,  it  is  now  generally  admitted  that 
hereditary  predisposition  is  a  most  important  factor  in 
the  determination  of  gout — that  persons  who  have  devel- 
oped gout  under  conditions  suitable  to  its  genesis  tend 
to  have  children  who  are  liable  to  develop  gout,  but  it 
does  not  follow  that  such  children  will  ever  suffer  from 
gout  unless  the  conditions  under  which  they  live  are  suit- 
able for  the  development  of  that  disease.  The  females 
of  gouty  families  frequently  escape  the  apparent  develop- 
ment of  gout  in  themselves,  but  transmit  the  disease,  or 
the  liability  to  it,  to  their  children.  It  is  doubtful,  how- 
ever, whether  true  atavism  occurs  in  connection  with  gout  ; 
that  is,  whether  gout  entirely  misses  a  generation.  It  is 
more  probable  that  it  appears  in  some  form,  irregular  or 
otherwise,  in  the  generation  that  it  is  supposed  to  have 
passed  over.  It  is  generally  admitted  that  parents  who 
have  become  gouty  under  conditions  of  ease  and  high 
living  tend  to  have  children  who  are  liable  to  develop 
gout  under  like  conditions.  But  it  must  not  be  assumed 
that  therefore  parental  high  living  is  a  cause  of  filial  gouti- 
ness.    The  diathesis,  the  inborn  tendency  to  acquire  the 


chak  vi]  Heredity.  103 

disease  under  certain  conditions,  is  transmissible  ;  but 
there  is  no  evidence  that  parental  high  living  increases 
that  tendency  in  the  child.  An  explanation  of  the  here- 
ditary character  of  gout  is  that  the  defects  of  the  cells  (pos- 
sibly the  cells  of  the  intestinal  mucosa)  of  the  progenitor 
are  transmitted  to  those  of  the  offspring  through  the  ovum 
or  the  spermatozoa. 

Scudamore  states  that  out  of  523  gouty  patients,  59 
per  cent,  gave  a  history  of  the  disease  in  the  parents  or 
grandparents.  Sir  Alfred  Garrod  found  that  the  predisposi- 
tion was  inherited  in  50  per  cent,  of  his  hospital  patients, 
but  among  his  private  cases  he  believed  that  the  tendency 
was  inherited  in  75  per  cent. 

Heredity  as  a  predisposing  factor  in  the  causation  of 
gout  stanjds  out  more  prominently  in  this  than  in  any  other 
country.  Amongst  the  poorer  classes  it  is  difficult  to 
obtain  reliable  information  as  to  the  inheritance  of  gout. 
I  have,  therefore,  taken  from  my  case-books  300  consecu- 
tive cases  of  gout,  in  all  of  which  careful  inquiry  had  been 
made  into  the  family  histories.  These  cases  were  all 
private  patients  belonging  to  the  well-to-do  classes. 

Of  the  300  cases,  244  gave  a  definite  family  history  of 
gout,  12  cases  gave  a  history  of  what  was  described  as 
rheumatism  in  parents  or  grandparents,  and  in  44  cases  no 
history  of  any  joint  disease  occurring  in  any  members  of 
the  family  could  be  obtained.  As  regards  the  12  cases 
which  gave  a  family  history  of  what  was  called  rheumatism, 
it  is  possible  that  the  disease  which  actually  occurred  in 
the  ancestors  was  gout  ;  but  these  cases  have  not  been 
included  among  those  with  a  definite  family  history  of 
gout. 

If  these  figures  are  reduced  to  percentages  the  following 
numbers  are  obtained  : — 

Definite  family  history  of  gout  .  .  .        r.      8i'3  per  cent. 

Family  history  of  what  was  called  rheumatism  .       4-0       ,,     ,, 
No  family  history  of  either  gout  or  rheumatism       14  "7       ,,     .. 


104       GOUT:    .ETIOLOGY   AND   VARIETIES.  [Part  n 

Of  the  cases  that  gave  a  definite  family  history  of  gout 
the  following  is  the  distribution  of  the  heritage  : — 

TABLE    XIII. 

From  one  or  both  parents  only  .  .  .24-6  per  cent. 

From  one  or  more  grandparents  only  .  •      17-6 

From  one  or  more  grandparents  and  one  or  both 

parents        .  •  .  .  .  .  .      i6-8 

From  one  or  both  parents,  and  other  members  of 

the  family  (not  grandparents)       .  .  .15-6 

From  one  or  more  grandparents,  and  other  mem- 
bers of  the  family  (not  parents)  .  .  .       9-4 

From  one  or  more  grandparents,  from  one  or  both 

parents,  and  other  members  of  the  family    .       9-0 

From  members  of  the  family  not  grandparents  or 

parents        .  .  .  .  .  .  .       7-0 

If  this  table  is  examined  it  will  be  seen  that  in  27  per 
cent,  of  the  cases  the  disease  was  transmitted  from  grand- 
parents to  grandchildren  without  the  fathers  or  mothers 
suffering  from  active  gout. 

Of  the  cases  inherited  from  the  parents  only,  the  follow- 
ing is  the  distribution  of  the  heritage  : — 

From  the  father  only  .  .  .  .  .73-4  per  cent. 

From  the  mother  only        .  .  .  .  .      ii-6       ,,     ,, 

From  both  parents    .  .  .  .  .  .15-0       ,,,, 

Of  the  cases  inherited  from  the  grandparents  only  the 
following  is  the  distribution  of  the  heritage  : — 

Paternal  side     .  .  .  .  .  .  •      53*5  per  cent. 

Maternal  side    .  .  .  .  .  .  ,21-0,,,, 

Both  sides  .  .  .  .  .  ,  .      25-5       ,,     ,, 

Habits  of  life. — The  abuse  of  alcoholic  drinks,  especially 
those  of  the  fermented  class,  such  as  wines  and  beers,  and 
the  excessive  consumption  of  nitrogenous,  rich,  and  in- 
digestible food,  are  powerful  factors  in  the  development  of 
gout.  Indolent  habits,  inadequate  physical  exercise,  and 
deficient  food,  with  bad  hygienic  surroundings,  also 
strongly  predispose  to  gout. 


Chap.  VI.]  HABITS    OF    LIFE.  105 

Gout  is  more  common  among  the  rich  than  the  poor, 
and  has  been  called  "  morbus  divitum  "  in  consequence. 
Over-feeding  and  luxurious  habits  of  life  undoubtedly 
favour  its  onset  ;  yet  it  may  occur  in  the  most  abstemious 
at  times,  and  the  poor  are  not  exempt  from  it.  It  might 
seem  that  the  poor  who  suffer  from  gout  would  afford  more 
favourable  subjects  in  whom  to  study  its  causation  than 
the  rich,  on  account  of  the  less  varied  nature  of  their  dietary 
and  conditions  of  life.  Some  writers  incline  to  the  view 
that  there  is  one,  and  only  one,  source  of  the  disease  among 
the  labouring  classes — malt  liquors.  It  can  hardly  be 
doubted  that  this  class  of  beverages  constitutes  at  least  a 
potent  exciting  cause  of  gout.  The  comparative  infre- 
quency  of  indulgence  in  malt  liquors  by  women  may  ac- 
count for  the  smaller  incidence  of  gout  on  this  sex,  while 
the  prevalence  of  the  disorder  in  England  as  opposed  to 
the  Continent  may  also  be  due  to  the  nature  of  our  prevail- 
ing beverage. 

Lead-poisoning. — Chronic  lead-poisoning  predisposes  to 
gout.     This  subject  will  be  fully  dealt  with  later  on. 

Influence  of  other  diseases. — Among  these  conditions 
it  is  interesting  to  bear  in  mind  the  influence  of  other  acute 
febrile  diseases  on  gout.  Many  years  ago  Braun  pointed 
out  that  gouty  patients  often  remain  for  a  long  time  free 
from  paroxysms  after  a  febrile  malady,  of  however  foreign 
a  nature  ;  and  among  recent  writers  Henry  M.  Lyman 
shows  that  various  acute  febrile  diseases  and  inflammations 
like  tonsillitis,  bronchitis,  rheumatism,  etc.,  afford  great 
relief  from  the  constitutional  symptoms  of  arthritis. 

Hare's  view  is  that  these  observations  go  to  prove  that 
the  relief  attained  is  due  to  the  increase  in  the  rate  of  com- 
bustion associated  with  pyrexia.  Acute  gout  itself  is  a 
pyrexia,  and  the  increase  in  combustion  and  carbonic  acid 
evolution  has  been  demonstrated  by  Magnus  Levy.  Hence 
the  improvement  which  succeeds  the  attack  is,  as  a  rule, 
proportionate  to  the  degree  of  febrile  reaction,  and  drugs 


io6       GOUT:    ETIOLOGY   AND   VARIETIES,  [part  ii. 

which  cut  short  the  pyrexia  tend  to  prevent  the  ameliora- 
tion in  general  health,  and  to  shorten  the  ensuing  period 
of  freedom  from  arthritic  attacks  which  commonly  follow 
the  uninterrupted  attack. 

Immediate  exciting  cause. — An  attack  of  acute  gout 
is  frequently  induced  by  unusual  indulgence  in  food  or 
drink,  or  by  some  powerful  emotion — such  as  a  fit  of  anger, 
worry,  or  anxiety,  or  by  exposure  to  cold,  or  by  the  receipt 
of  some  injury. 

Clinical  features  of  acute  gout. — A  slow  deposition  of 
sodium  biurate  within  the  joints,  accompanied  by  twinges 
of  pain,  may  occasionally  precede  the  acute  attack  ;  but, 
as  a  rule,  no  warning  ushers  in  the  first  attack  of  gout,  and 
the  individual  usually  feels  in  good  health  just  prior  to  the 
attack.  Subsequent  attacks,  however,  may  be  preceded 
by  symptoms  of  dyspepsia,  constipation,  mental  depres- 
sion, or  loss  of  appetite. 

The  seizure  of  acute  gout  most  frequently  occurs  in 
the  early  hours  of  the  morning,  but  may  come  on  at  any 
hour  of  the  day  or  night.  Usually  between  the  hours  of 
one  and  four  in  the  morning  the  patient  is  awakened  by 
severe  pain,  generally  in  the  great  toe,  sometimes  in  the 
ankle,  instep,  heel,  or  knee.  Slight  shivering  attacks  and  a 
little  elevation  of  temperature  may  follow.  The  pain  in- 
creases in  intensity,  so  that  the  slightest  jarring  of  the 
affected  part  may  cause  extreme  torture.  After  some  hours, 
partial  abatement  of  the  pain  occurs,  and  is  accompanied 
by  gentle  perspiration.  In  the  morning  the  toe  is  swollen, 
and  the  skin  over  the  affected  joint  is  of  an  intense  red 
colour,  or  purple-red,  or  a  livid-red,  contrasting  with  the 
pale  red  or  rose  colour  of  the  skin  over  the  affected  joints 
in  cases  of  acute  articular  rheumatism.  The  discoloured 
skin  is  tense,  shiny,  and  extremely  tender,  and  the  veins 
are  distended.  The  extreme  pain  to  touch  over  the  joint 
affected  with  acute  gout  is  in  marked  contrast  to  the 
much  less  painful  reaction  to  touch  over  the  joint  affected 


Chap.  VI.]  ACUTE    GOUT.  107 

with  acute  rheumatism.  On  the  second  night  the  severity 
of  the  pain  may  recur,  and  such  recurrences  may,  in  the 
absence  of  suitable  treatment,  occur  for  many  days.  The 
pain  in  the  joint  is  excruciating,  and  is  quite  out  of  propor- 
tion to  the  external  signs  of  inflammation.  When  the 
attack  is  subsiding  the  swelling  and  redness  of  the  affected 
part  lessen,  the  skin  itches  and  pits  on  pressure,  and  des- 
quamation follows.  Sir  Willoughby  Wade  *  has  pointed 
out  that  in  an  acute  attack  of  gout  in  the  great  toe  a  line  of 
tenderness  extends  from  the  base  of  the  great  toe  across 
the  foot  to  the  outer  side.  This  line  is  the  site  of  a  nerve- 
trunk,  which  is  distributed  to  the  periphery  of  the  great 
toe.  The  cause  of  the  tenderness  is  probably  due  to  a 
deposition  of  sodium  biurate  in  the  nerve  sheath,  or  in  the 
nerve  itself.  The  oedema  around  the  joint  is  characteristic, 
and  is  of  great  assistance  in  distinguishing  the  affection 
from  rheumatism.  Gouty  inflammation  of  a  joint  is  not 
followed  by  suppuration.  The  temperature  most  com- 
monly ranges  from  99°  to  102°  F.,  and  the  attack  is  gener- 
ally accompanied  by  thirst,  anorexia,  and  constipation, 
whilst  the  urine  is  scanty,  high-coloured,  and  usually  de- 
posits amorphous  urates  on  cooling.  In  very  severe 
attacks  of  acute  gout  a  temperature  as  high  as  I05"8  has 
been  recorded ;  such  an  abnormal  elevation  of  temperature 
is  frequently  accompanied  by  severe  vomiting.  Both 
conditions  point  to  a  profound  toxsemia.  Temporary  albu- 
minuria has  been  frequently  observed  during  the  early 
stages  of  an  attack  of  acute  gout,  and  occasionally  slight 
albuminuria  lasts  throughout  the  attack.  The  pulse  is 
generally  full  and  of  high  tension,  but,  apart  from  the  acute 
attacks,  my  experience  is  that  arterial  tension  is  not  much 
higher  in  gouty  individuals  than  in  other  persons  of  the 
same  age. 

An  attack  of  acute  gout  lasts  on  an  average  from  eight 
to  fourteen  days  in  persons  of  strong  constitution,  but  with 

*  Brit.  Med.  Journ.,  1897,  i. 


io8        GOUT:    ETIOLOGY   AND  VARIETIES.  [Part  ii 

advancing  age  the  duration  of  the  attack  becomes  pro- 
longed. A  first  attack  of  gout  may  not  be  followed  by 
another,  provided  attention  be  paid  to  diet  and  to  the 
general  mode  of  life.  On  the  other  hand,  frequent  recur- 
rences may  supervene.  At  first  the  attack  of  gout  is  most 
liable  to  occur  towards  the  end  of  winter  or  beginning  of 
spring,  but  after  repeated  annual  attacks  at  the  period 
mentioned,  autumnal  attacks  may  be  added,  or  even,  in 
exceptional  cases,  summer  attacks.  Although  the  majority 
of  first  attacks  of  gout  occur  in  the  great-toe  joint,  yet  the 
disease  may  start  in  other  joints,  of  which  those  most  com- 
monly so  affected,  placing  them  in  their  order  of  liability 
to  such  attacks,  are  the  ankles,  the  knees,  the  small  hand- 
joints,  the  elbows,  and,  rarely,  the  shoulders  and  hips.  The 
selection  of  any  particular  joint  for  a  primary  attack  is  no 
doubt  dependent  on  slight  inflammatory  or  trophic  changes 
in  the  particular  joint  from  some  recent  injury  or  strain. 

Cases  of  typical  acute  gout  are  now  much  less  frequent 
than  they  were  in  the  days  when  the  disease  was  so  graphic- 
ally described  by  Sydenham.  This  is  mainly  due  to  the 
greater  temperance  in  eating  and  drinking  which  prevails 
in  the  present  age,  and  in  part,  no  doubt,  to  the  spread  of 
athleticism,  and  to  the  development  of  healthy  outdoor 
exercises.  Still,  in  many  cases  the  faults  of  the  ancestors 
have  transmitted  to  their  descendants  a  tendency  to  the 
minor  forms  of  gout,  which  frequently  require  treatment  at 
the  hands  of  the  physician. 

Transient  albuminuria  occurs  in  gout,  especially  during 
the  acute  attacks.  The  frequency  of  its  occurrence  and 
its  amount  furnish  an  index  of  the  degree  of  renal  in- 
adequacy. Transient  glycosuria  also  occurs,  and  may  be 
regarded  as  evidence  of  hepatic  inadequacy. 

Clinical  features  of  chronic  g-out. — In  the  earlier 
attacks  of  gout  it  is  not  usual  for  more  than  one  or  two 
joints  to  be  affected,  but  after  repeated  seizures  a  number  of 
joints  may  become  involved.     As  the  recurrence  of  gout 


Chap.  VI.]  CHRONIC    GOUT.  109 

becomes  more  frequent  the  attacks  also  become  more  pro- 
longed, and  last  for  weeks  or  even  months  unless  efficacious 
treatment  is  resorted  to.  In  chronic  gout  the  deposits  of 
sodium  biurate  linger  in  the  joints,  leading  to  deformities 
and  crippling  of  the  parts.  Slight  recurrences  readily 
occur,  and  various  forms  of  irregular  gout  may  then  be- 
come added  to  the  gouty  condition. 

In  the  subjects  of  chronic  gout  tophi  are  apt  to  form  in 
various  localities  ;  these  deposits  are  most  frequently  seen 
in  the  male  sex,  and  constitute  the  so-called  tophaceous  gout. 
These  tophi  consist  mainly  of  deposits  of  sodium  biurate 
under  the  skin,  and  are  principally  found  in  the  auricles 
of  the  ears,  in  the  vicinity  of  joints,  and  in  bursae  over 
joints.  If  excessive  accumulation  of  the  biurate  occurs, 
these  tophi  assume  a  great  size,  and  may  then  cause  the  in- 
tegument to  give  way,  when  a  discharge  of  a  thick  creamy 
fluid  containing  an  abundance  of  crystals  of  sodium  biurate 
takes  place.  The  swelling  in  the  vicinity  of  a  joint  may 
give  rise  to  fluctuation,  but  such  swelling  should  never 
be  opened.  Tophi  may  communicate  with  a  joint,  or  may 
be  situated  beneath  the  skin  and  remote  from  a  joint. 
Occasionally  they  are  present  in  large  size  in  the  vicinity 
of  a  joint,  which  otherwise  appears  free  from  the  disease 
and  whose  mobility  is  unimpaired. 

In  connection  with  chronic  gout  considerable  enlargement 
and  deformity  of  joints  may  occur  to  which  the  deposits 
of  sodium  biurate  only  contribute  in  small  part.  In  such 
cases  the  enlargement  is  due  to  thickening  of  the  synovial 
membrane,  and  to  overgrowth  of  the  cartilages  and  of  the 
ends  of  the  bones.  This  form  constitutes  the  so-called 
chronic  deforming  gout.  Permanent  deformity  of  the  af- 
fected joints  may  result,  and  partial  dislocations  and  anky- 
loses may  also  occur.  On  the  other  hand,  the  uratic  de- 
posits may  undergo  complete  solution,  and  the  joint  be 
left  in  an  apparently  normal  condition. 

The    kidneys    in    chronic    gout. — The  urine  of  chronic 


no        GOUT:    ^.TIOLOGY  AND  VARIETIES,   [part  ii. 

gout  is  somewhat  increased  in  quantity,  and  is  of  lower 
specific  gravity  and  somewhat  paler  than  normal.  The 
amount  of  uric  acid  eliminated  is  diminished.  A  trace  of 
albumen  is  frequently  present,  and  permanent  albuminuria 
is  a  fairly  common  occurrence  in  confirmed  gout.  If  the 
renal  condition  is  allowed  to  become  very  aggravated,  then 
cardiac  failure  follows,  with  pulmonary  congestion,  cedema 
of  the  lungs,  bronchitis,  congestive  enlargement  of  the  liver, 
gastric  catarrh,  dropsy,  and  symptoms  of  uraemia.  In 
such  cases  pneumonia  is  apt  to  supervene  and  to  be  attended 
by  a  fatal  issue. 

Changes  in  the  heart  and  circulation,  consequent  on 
gouty  affections  of  the  kidneys,  are  indicated  by  hyper- 
trophy of  the  left  ventricle,  a  strong  cardiac  impulse,  dis- 
placement of  the  apex  beat  to  the  left,  loudness  and  occa- 
sional reduplication  of  the  first  sound,  and  accentuation  of 
the  aortic  second  sound.  The  pulse  is  of  high  tension,  and 
the  arteries  are  hard,  tortuous,  and  sometimes  atheromat- 
ous. Under  such  conditions  a  cerebral  haemorrhage  may 
occur.  If  compensation  fails,  then  dilatation  of  the  heart 
occurs,  the  area  of  dulness  is  greatly  increased,  the  action 
of  the  heart  becomes  rapid,  and  the  usual  signs  of  back- 
working  of  the  blood  from  the  left  side  of  the  heart  follow. 

Although  granular  kidney  is  fairly  common  in  connec- 
tion with  chronic  gout,  yet  it  is  not  invariably  present. 
Certainly  some  patients  may  have  gout  and  never  develop 
granular  kidney,  and  on  the  other  hand  some  may  have 
granular  kidney  and  never  gout ;  so  that,  however  close  the 
relation  may  be,  it  is  not  constant  or  essential.  As  West 
has  pointed  out,  gout  and  granular  kidney  are  both  of 
them  very  common  affections,  and  sufficiently  common  to 
be  not  infrequently  associated  accidentally  without  any 
causal  connection.  Still,  making  allowance  for  this,  the 
association  seems  altogether  more  common  than  mere 
coincidence  could  account  for. 

In  men  in  the  fifth  and  sixth  decades  albuminuria,  apart 


Chap.  VI.]  GRANULAR    KIDNEY.  iil 

from  gout,  is  by  no  means  infrequent  and  not  always  seri- 
ous. It  is  probably  the  expression  of  pre-senile  changes  in 
the  kidneys.  The  albuminuria  and  the  number  and  variety 
of  the  casts  are  not  of  as  much  importance  in  prognosis  as 
are  other  factors.  The  facts  indicative  of  serious  disease 
are  : — (i)  Persistent  low  specific  gravity  of  the  urine  (1008 
to  1012)  ;  (2)  marked  arterial  sclerosis,  with  the  apex  beat 
an  inch  or  two  outside  the  nipple  line,  and  a  ringing  accent- 
uated aortic  second  sound ;  and  (3)  albuminuric  retinitis.  A 
trace  of  albuminuria  and  a  few  casts  are  the  danger  signals. 

West  concludes,  with  respect  to  the  relationship  of  both 
gout  and  lead  to  granular  kidney,  that,  though  each  may 
produce  chronic  changes  in  the  kidney,  neither  causes 
granular  kidney  ;  but  the  presence  of  granular  kidney  greatly 
increases  the  liability  of  the  patient  to  gout  on  the  one  hand 
and  lead-poisoning  on  the  other,  or  to  both  together,  and 
in  each  affection  alike  greatly  increases  the  gravity  and  risk. 

Croftan  *  states  that  he  has  demonstrated  that  both 
xanthin  and  hypoxanthin,  when  injected  hypodermically 
in  the  strength  of  0.3  to  0.7  per  cent,  watery  solution  for  a 
period  of  several  months,  produce  granular  degeneration 
of  the  epithelial  cells  lining  the  convoluted  tubules  and  a 
proliferation  of  the  endothelium  of  the  intertubular  capil- 
laries. Albuminuria  invariably  occurred  after  a  period  of 
three  months,  so  that  he  concludes  that  the  presence  of 
minute  quantities  of  purin  bases  in  the  circulation  is  cap- 
able of  producing  marked  kidney  changes.  He  has  com- 
pared these  changes  with  those  of  chronic  lead  poisoning, 
and  finds  that  they  are  identical.  As  he  considers  that  the 
kidney  changes  of  gout  are  identical  with  those  of  chronic 
lead-poisoning,  he  infers  that  the  organic  kidney  changes 
in  gout  may  "be  produced  by  purin  bases.  On  the  other 
hand,  he  finds  that  uric  acid  injected  into  the  circulation 
of  healthy  animals  for  a  period  of  over  three  months  pro- 
duces no  kidney  changes  whatever. 

*  Journ.   of  American  Med.  Association,  1899. 


CHAPTER    VII. 
THE   URINE   AND   URIC   ACID. 

The  urine  in  gout — Uric  acid  excretion — Uric  acid  and  urea 
elimination — The  amorphous  urate  deposit — Estimation  of 
uric  acid — Gowland-Hopkins  method — Otto  Folin  method — 
Methods   of  Dimmock  and  Branson — Plumbism  and  gout. 

The  urine  in  g'Out. — Considerable  difference  of  opinion 
exists  as  to  whether  the  excretion  of  uric  acid  is  dimin- 
ished both  during  the  paroxysm  of  acute  gout  and  in 
connection  with  chronic  gout. 

The  uric  acid  theory  was  to  a  great  extent  based  on 
the  view  held  by  Sir  Alfred  Garrod  that  the  excretion  of 
uric  acid  is  diminished  during  the  paroxysm,  this  being 
associated  with  a  retention  of  uric  acid  in  the  system.  The 
results  obtained  by  different  observers  as  to  the  excretion 
of  uric  acid  in  cases  of  gout  will  therefore  be  considered. 

Pfeiffer*  compared  the  quantities  of  uric  acid  contained  in 
the  urine  of  gouty  patients  at  various  ages,  in  whom  the  com- 
plaint had  not  yet  become  chronic,  with  the  quantities  con- 
tained in  the  urines  of  healthy  subjects  at  the  same  age.  For 
purposes  of  comparison  the  quantities  of  uric  acid  found  by 
him  were  calculated  in  grammes  per  lOO  kilogrammes  of  the 
body-weight.     His  results  were  as  follows: — 


Age. 

Gouty  subject. 

Healthy  subject. 

30  to  40 
40   to    50 
50  to   60 
60  to   70 

0.885  grm. 
0.818     ,, 
0.701      ,, 
0.661      ,, 

0.965  grm. 
0.882     „ 

0.752     ,. 

*  Berlin,  klin.  Woch.,  1892. 
112 


CAP.  VII.]  URIC    ACID    EXCRETION.  113 

These  results  indicate  that  the  amounts  of  uric  acid  ex- 
creted by  gouty  subjects  were  always  rather  lower  than  the 
quantities  excreted  by  healthy  persons  of  the  same  age. 

J.  Fawcett  *  has  examined  the  urine  of  a  series  of 
patients  with  gout,  estimating  the  uric  acid  by  the  Gow- 
land-Hopkins  process.  He  found  that  the  amount  of  uric 
acid  excreted  was  very  variable,  but  that  in  the  majority 
of  cases  it  was  distinctly  below  the  average  excreted  by  a 
healthy  man  on  a  similar  diet.  During  acute  attacks  there 
was  an  increased  output  of  uric  acid,  which  was  usually 
most  marked  towards  the  end  of  the  attack.  The  uric  acid 
excretion  did  not  vary  inversely  to  the  acidity  of  the  urine, 
nor  was  there  any  definite  relationship  between  the  quan- 
tity of  urine  passed  and  the  amount  of  uric  acid  excreted. 

In  the  following  table  are  the  results  of  the  daily  deter- 
minations that  I  made  for  eight  successive  days  respect- 
ively of  the  total  uric  acid  excretion  in  the  urine  of  three 
persons,  viz.  (a)  a  male  patient  suffering  from  an  attack 
of  subacute  gout  supervening  on  chronic  gout  ;  (b)  a. 
male  patient  suffering  from  chronic  gout  and  lead-poisoning, 
with  recent  pain  in  the  right  metatarso-phalangeal  joint 
and  in  both  ankle  joints  ;  (c)  a  healthy  man.  The  quan- 
tities of  uric  acid  in  the  three  cases  are  given  in  grammes, 
and  are  calculated  per  100  kilogrammes  of  the  body-weight. 
All  the  individuals  were  between  forty  and  fifty  years  of  age. 

TABLE    XIV. 

Showing  the  daily  elimination  of  uric  acid  in  (a)  a  case  of  subacute 
gout  ;  (b)  a  case  of  chronic  gotit  and  plumbism  ;  {c)  a  healthy 
person.  Quantities  of  uric  acid  given  in  grammes  per  100  kilo- 
grammes of  the  body-weight.  All  the  individuals  between  forty 
and  fifty  years  of  age. 


Subacute  gout. 

Chronic  gout. 

Healthy  subject. 

0.260  grm. 
0.263      „ 
0.315      » 

0.578  grm. 
0.617      ,, 
0.665      ,, 

1 .  105   grm. 
1.027      ,, 
1.020     ,, 

*  Guy's  Hosp.  Reports,   1895,  vol.  Iji. 


114        GOUT  :    iETIOLOGY  AND  VARIETIES,  [part  ir. 


TABLE  XIV.   {continued). 


Subacute  gout. 

Chronic  gout. 

Healthy  subject. 

0.350  grm. 

0.715   grm. 

1.376  grm 

0.442      „ 

0.443     >, 

1. 175      .. 

0.556     ,. 

0.372     ,, 

1.030     „ 

0.506     ,, 

0.593     .. 

1.252     ,, 

0.494     .. 

0.594     „ 

1-203      „ 

0.398      ,, 

0.572     „ 

1. 148      ,, 

(average) 

(average) 

(average) 

On  the  other  hand,  detailed  analyses  of  the  urine  were 
made  in  two  cases  of  typical  gout  by  Chalmers  Watson,  a 
daily  examination  of  the  urine  being  made  for  many  weeks. 
The  results  of  this  investigation  showed  no  disturbance  in 
the  uric  acid  elimination  either  before,  during,  or  after  the 
paroxysm. 

Chalmers  Watson  has  also  recorded  a  series  of  observa- 
tions, the  results  showing  an  actual  increase  of  uric  acid 
excretion  during  the  attack  of  gout. 

From  the  analyses  made  by  a  number  of  observers 
Minkowski  states  that  the  following  conclusions  may  be 
drawn  : — (i)  The  daily  excretion  of  uric  acid  in  the  inter- 
vals between  acute  attacks  ranges  within  the  same  limits 
as  does  the  excretion  in  healthy  individuals.  (2)  In 
chronic  gout,  even  in  those  cases  in  which  there  is  marked 
deposition  of  biurates  in  the  tissues,  a  constant  variation 
from  the  normal  amount  of  uric  acid  excretion  in  any  one 
direction  has  not  been  definitely  proved.  (3)  Immediately 
preceding  an  acute  attack  there  is  regularly  a  diminution 
in  the  amount  of  uric  acid  eliminated  in  the  urine,  whereas 
during  and  after  the  attack  the  uric  acid  output  is  increased. 
Futcher's  analyses  in  a  number  of  cases  fully  accord  with 
the  statement  contained  in  section  3,  but  they  differ  materi- 
ally from  those  stated  in  section  2.  He  almost  always  found 
a  marked  diminution  in  the  uric  acid  excreted  in  the  inter- 
vals between  acute  attacks  in  chronic  tophaceous  gout. 


chap.vii]  uric    acid    excretion.  115 

Ratio   of   uric   acid  elimination   to   that  of   urea.— 

Haig  has  advanced  the  theory  that  normally  there  is  a 
constant  ratio  of  i  to  35  between  the  uric  acid  and  urea 
formation,  and  that  if  the  uric  acid  excretion  falls  below 
this  ratio  it  is  due  to  the  retention  and  storage  of  uric  acid 
in  the  liver,  spleen,  kidneys,  joints,  and  fibrous  tissues, 
whereas  an  increase  in  the  proportion  of  uric  acid  to  urea 
is  due  to  the  washing  out  from  its  storage  places  of  the 
deposited  uric  acid.  According  to  this  view,  the  amount 
of  uric  acid  produced  in  relation  to  urea  in  each  individual 
is  a  constant  factor,  the  variations  in  the  amounts  eliminated 
being  due  on  the  one  hand  to  excessive  storage,  and  on  the 
other  to  the  discharge  of  the  stored-up  supply. 

This  theory  of  the  existence  of  a  normal  ratio  of  uric 
acid  to  urea,  and  of  every  departure  from  it  being  due  to 
a  pathological  cause,  is  disproved  by  the  following  experi- 
ments : — (i)  Bleibtreu  and  Schultze,*  experimenting  on 
themselves,  showed  that  the  ratio  between  uric  acid  and 
urea  can  be  considerably  altered  by  means  of  the  diet  with- 
out the  general  health  being  influenced.  (2)  Herringham 
and  Groves, t  as  the  result  of  a  series  of  experiments  that 
they  made,  entirely  fail  to  corroborate  Dr.  Haig's  observa- 
tions, and  think  that  either  what  was  true  for  his  system 
was  not  true  for  theirs,  or  that  Dr.  Haig's  results  were, 
to  quote  their  own  words,  "  inaccurate  and  deceptive  owing 
to  his  having  employed  a  very  uncertain  and  inaccurate 
method  for  the  estimation  of  uric  acid."  (3)  The  follow- 
ing results  of  the  determinations  which  I  have  made  of  the 
total  daily  eliminations  of  uric  acid  and  urea  in  the  urine 
of  a  healthy  adult  man,  and  which  consist  of  observations 
extending  over  a  period  of  fifty  days,  show  that  the  ratio 
of  uric  acid  to  urea  varied  from  i  :  28  to  i  :  55  (the  average 
being  i  :  42),  although  throughout  the  entire  period  the 
individual  remained  in  good  health. 

*  Pfluger's  Archiv,  Bd.  xlv. 
t  Journ.  of  Physiology,  1891. 


Ii6       GOUT  :    ETIOLOGY    AND    VARIETIES,  [part  ii. 

TABLE    XV. 

Fifty  daily  eliminations  of  uric  acid  and  urea  of  a  healthy  adult  man 
on  a  mixed  diet. 


No.  of  oz.  of 

Uric  acid  excreted 

Urea  excreted  per          Ratio  of  uric 

urine  per  diem. 

per  diem  (gramme). 

diem  (grammes).           acid  to  urea. 

63 

0.654 

28.34                         i: 

43 

68 

0.714 

31.62                         i: 

44 

72 

0.626 

29.82                          I  : 

47 

42 

0.532 

29.39                          i: 

55 

61 

0.819 

30.19                          l: 

2>7 

56 

0.663 

25.22                          I  : 

38 

65 

0.616 

27.67                          l: 

45 

59 

0.612 

24.44                         I  : 

40 

41 

0.826 

30.32                         i: 

37 

57 

0.705 

21 .91                          I  : 

31 

49 

0.618 

31.27                         i: 

50 

63 

0.751 

27.57                          l: 

37 

48 

0.722 

28.89                          I  • 

40 

64 

0.569 

23.44                         i: 

41 

51 

0.652 

29.89                          I  : 

46 

60 

0.608 

27.00                          I  • 

44 

56 

0.591 

27.71                          I 

47 

50 

0.561 

27-54                       I 

49 

60 

0.630 

27.91                       I 

44 

45 

0.742 

26.56                       I 

36 

45 

0.550 

23.60                       I 

40 

60 

0.640 

31-34                        I 

49 

61 

0.581 

28.34                        I 

49 

61 

0.537 

22.35                        I 

41 

64 

0.572 

26.49                        I 

46 

53 

0.595 

21.24                        I 

36 

55 

0.764 

24-73                        I 

32 

69 

0.637 

28.58                        I 

=  45 

63 

0.526 

23.13                        I 

:44 

72 

0.583 

28.88                        I 

:49 

45 

0.620 

24.26                        I 

:  39 

45 

0.698 

28.01                        I 

:40 

52 

0.680 

30.04                        I 

:44 

69 

0.705 

33--^^                        I 

:47 

40 

0.837 

25.62                        I 

:  31 

42 

0.728 

30.54                        I 

:42 

67 

0.665 

30.11                        I 

=  45 

44 

0.550 

29.50                        I 

:  53 

54 

0.554 

29.88                        I 

:  54 

62 

0.582 

26.13                        I 

=  45 

55 

0.515 

22.15                        I 

:43 

55 

0.632 

27.14                        I 

:43 

54 

0.585 

28.34                        I 

=  48 

chap.vii.]     amorphous  urate  deposit. 

TABLE   XV.  (continued). 


117 


No.  of  oz.  of 

Uric  acid  excreted 

Urea  excreted  per 

Ratio  of  uric 

urine  per  diem. 

per  diem  (gramme). 

diem  (grammes). 

acid  to  urea. 

66 

0.776 

28.05 

36 

49 

0.536 

25  .20 

47 

67 

0.560 

23.56 

42 

45 

0.550 

21.63 

39 

35 

0.660 

23.10 

35 

55 

0.624 

23.09 

37 

87 

0.691 

19.76 

28 

TABLE    XVI. 


Excretion    of 
uric  acid. 

Excretion  of 
urea. 

Ratio  of  uric 
acid  to  urea. 

Daily      average       in 

grammes 
Daily       average       in 

grains 
Average  in   24  hours 

for  each  lb.  of  body 

weight    (in    grains) 

0.639 
9.8 

0.07 

26.89 
415.0 

3.19 

I  :  42 
I  :  42 

It  is  evident  from  the  above  results  that  no  constant 
ratio  exists  in  a  given  individual  between  the  excretion  of 
uric  acid  and  urea. 

Amorphous  urate  deposit  of  urine.  —  Sir  William 
Roberts  *  has  shown  that  the  amorphous  urate  deposit  of 
human  urine  is  of  the  same  composition  as  the  solid  or 
semi-solid  urinary  excrement  of  birds  and  serpents,  the 
only  difference  being  one  of  physical  form.  The  deposit 
from  human  urine  is  amorphous,  whilst  the  urinary  excre- 
ment of  birds  and  serpents  consists  of  minute  crystalline 
spheres.  Sir  William  Roberts  shows  that  this  difference 
in  physical  form  is  a  mere  accident  of  molecular  aggrega- 
tion, since,  under  certain  conditions,  the  amorphous  urate 
deposit  can  be  transformed  into  crystalline  spheres,  whilst 

*  Croonian  Lectures  en  "  Uric  Acid  Gravel  and  Gout,"   1892. 


ii8       GOUT:    ETIOLOGY    AND    VARIETIES.  [Part  ii. 

the  crystalline  urinary  substance  of  birds  and  serpents  can 
be  converted  into  amorphous  deposit.  Bence  Jones  *  was 
the  first  to  show  that  the  amorphous  urate  deposit  yielded 
to  water  a  soluble  moiety  consisting  of  true  biurate,  and 
left  a  sediment  consisting  of  pure  uric  acid,  and  from  the 
results  of  his  analyses  he  inferred  that  the  amorphous  urate 
deposit  consisted  of,  or  at  least  often  contained,  a  molecule 
of  biurate  in  loose  combination  with  a  further  molecule  of 
uric  acid.  Sir  William  Roberts  took  up  and  continued  the 
investigation  dropped  by  Bence  Jones  thirty  years  before, 
and  has  shown  that  a  third  order  of  uric  acid  salts — the 
quadriurates — exists,  and  that  the  amorphous  urate  deposit 
of  human  urine  and  the  urinary  excretion  of  birds  and  ser- 
pents belong  to  this  order,  and  consist  of  a  compound  of 
biurate  and  uric  acid  in  the  proportion  of  one  molecule  of 
each.  Sir  William  Roberts  concludes  that  the  quadriurates 
are  the  physiological  combinations  of  uric  acid. 

The  amorphous  urate  or  quadriurate  deposit  of  urine 
is  generally  referred  to  as  consisting  of  a  mixture  of  the 
potassium,  sodium,  ammonium,  and  calcium  urates.  As  far 
as  I  can  ascertain,  however,  no  quantitative  determination 
of  the  bases  in  the  deposit  has  yet  been  made.  The  near- 
est approach  to  it  is  an  analysis  made  by  Sir  William 
Roberts  f  of  a  sample  of  amorphous  urate  deposit  pre- 
pared by  an  artificial  process  with  potassium  carbonate, 
which  would  therefore  most  probably  contain  more  potas- 
sium than  the  natural  deposit.  I  therefore  considered 
it  advisable  to  determine  the  actual  bases  present  in 
the  amorphous  urate  deposit  and  their  relative  propor- 
tions. 

Composition  of  the  amorphous  urate  deposit  of 
urine. — The  deposit  was  obtained  from  several  gallons 
of  acid  urine  passed  by  patients  suffering  from  febrile 
diseases,  and  was  collected  on  a  filter  and  allowed  to  drain. 

*  Journ.  of  the  Chemical  Society,  1862,  vol.  xv. 

t  Croonian  Lectures  on  "  Uric  Acid  Gravel  and  Gout,"  1892,  p.  20. 


CHAr.viij       AMORPHOUS    URATE    DEPOSIT.  119 

It  was  decomposed  by  boiling  with  distilled  water  and  ex- 
cess of  hydrochloric  acid,  the  mixture  was  then  allowed  to 
cool,  filtered  from  the  deposited  uric  acid,  and  the  filtrate, 
which  then  contained  the  bases  in  the  form  of  chlorides, 
was  evaporated  to  dryness.  The  residue  was  taken  up 
with  distilled  water,  filtered  from  the  minute  amount  of 
uric  acid  left  in  solution  after  precipitation  of  the  bulk  of 
the  acid,  and  evaporated  to  dryness.  Part  of  the  residue 
was  submitted  to  qualitative  analysis,  and  found  to  contain 
ammonium,  sodium,  and  potassium,  with  very  small  traces 
of  calcium  and  magnesium.  The  amounts  of  ammonium, 
sodium,  and  potassium  were  then  estimated  in  the  usual 
manner  in  the  other  portion,  when  their  relative  quantities 
were  found  to  be  as  follows  : — • 

Paris  per  loo. 
Ammonium    .......  46 

Sodium  .  .  .  ,  .  .  .  40 

Potassium       .......  14 

These  amounts,  calculated  as  the  respective  quadriurates, 
would  approximately  give  the  following  composition  for 
the  amorphous  uratic  deposit  that  naturally  forms  in  acid 
febrile  urines  : — ■ 

7  molecules  NH,HC-H„N^O.,,  HX-H,N^O., — Ammonium    quadri- 

urate. 
5  molecules  NaHC-H,N,0  ,  H„C.H„N,0., — Sodium  quadriurate. 
I  molecule  KHC.H^N^O.,,  H^CgH^N^Oj, — Potassium  quadriurate. 

It  is  possible,  however,  apart  from  the  quadriurates, 
that  the  uric  acid  is  in  part  excreted  in  loose  combination 
with  some  other  organic  substance.  This  combination,  if 
it  exists,  is  probably  easily  broken  up,  and  the  uric  acid 
then  set  free. 

Estimation  of  uric  acid  in  urine. — Various  methods 
have  been  employed  for  the  estimation  of  uric  acid  in  the 
urine,  including  Heintze's  process,  Haycraft's  process, 
Fokker's  process,  Salkowski's  process,  and  Ludwig's  modi- 
fication  of   Salkowski's   process.     In    connection   with   all 


120       GOUT  :    ETIOLOGY    AND    VARIETIES,  [part  ii. 

these  processes  there  are  faults  or  objections  from  which 
the  following  processes  are  free. 

Gowland-Hopkins  method. — This  process  depends  upon 
the  fact  that  when  urine  is  saturated  with  ammonium 
chloride  all  the  uric  acid  is  precipitated  as  an  ammonium 
urate.  From  the  ammonium  urate  the  uric  acid  is  set 
free,  and  the  amount  of  it  is  determined  by  titration  with 
a  standard  solution  of  potassium  permanganate.  One 
great  advantage  of  this  process  is  that  there  is  no  danger 
of  the  reduction  of  the  ammonium  urate  as  there  is  of  the 
silver  urate  produced  in  some  of  the  other  processes  ;  more- 
over, the  ammonium  urate  is  easy  to  filter,  and  permits  of 
the  liberation  of  its  uric  acid  with  great  readiness.  Another 
great  advantage  of  the  process  is  that  although  xanthin  is 
at  first  precipitated  along  with  the  ammonium  urate,  yet 
the  subsequent  treatment  with  hydrochloric  acid  entirely 
removes  it,  so  that  finally  it  is  not  estimated  along  with  the 
uric  acid. 

The  process  is  worked  as  follows  : — ^To  lOO  c.c.  of  the 
urine  powdered  ammonium  chloride  is  added  till-  practical 
saturation  is  obtained  ;  about  30  grammes  of  ammonium 
chloride  as  a  rule  are  required.  When  a  small  quantity 
remains  undissolved,  after  brisk  stirring  for  a  few  minutes, 
saturation  is  sufficiently  complete.  The  urine  is  then  al- 
lowed to  stand  for  two  hours,  during  which  time,  if  possible, 
it  is  occasionally  stirred  to  promote  subsidence,  and  is 
then  filtered  through  thin  filter-paper,  and  washed  three  or 
four  times  with  a  saturated  solution  of  ammonium  chloride. 
The  filtrate  should  remain  perfectly  clear  and  bright.  The 
precipitated  ammonium  urate  is  then  washed  off  the  filter 
into  a  small  beaker  with  a  jet  of  hot  distilled  water,  and 
is  heated  just  to  boiling  with  an  excess  of  hydrochloric  acid. 
The  beaker  and  its  contents  are  allowed  to  stand  in  the 
cold  for  two  hours,  when  the  uric  acid  separates  out  com- 
pletely, and  is  then  collected  on  a  filter  and  washed  with 
cold    distilled    water.      The   filtrate    should   be    measured 


Chap.  VII.]         ESTIMATION    OF    URIC    ACID.  121 

before  the  washing  is  begun,  and  i  milligramme  added  to 
the  final  result  for  each  15  c.c.  of  filtrate  present — this  need 
never  be  more  than  20-30  c.c.  The  uric  acid  is  then  washed 
off  the  filter  with  hot  water,  warmed  with  sodium  carbonate 
till  dissolved,  and  made  up  with  water  to  100  c.c.  The 
liquid  is  now  transferred  to  a  flask,  20  c.c.  of  strong  pure 
sulphuric  acid  are  added,  and  the  mixture  is  immediately 
and  while  warm  titrated  with  one-twentieth  normal 
potassium  permanganate  solution.  The  latter  should  be 
added  slowly  towards  the  end  of  the  reaction,  the  close  of 
which  is  marked  by  the  first  appearance  of  a  pink  colour, 
which  is  permanent  for  an  appreciable  interval.  Previously 
the  disappearance  of  the  colour  is  instantaneous.  The 
permanganate  solution  is  made  by  dissolving  1.578 
grammes  of  pure  potassium  permanganate  in  a  litre  of 
distilled  water,     i  c.c.  =  "00375  gramme  of  uric  acid. 

Otto  Folin  method. — It  is  contended  that  the  method 
of  Otto  Folin  is  a  more  accurate  method  than  that  of  Gow- 
land-Hopkins  for  the  estimation  of  uric  acid  in  urine. 
The  following  is  the  process  : — Take  100  c.c.  of  urine,  add 
10  grammes  of  ammonium  sulphate,  render  it  slightly 
alkaline  with  ammonia,  shake,  and  set  aside  for  two  hours. 
Collect  the  precipitated  ammonium  urate  on  a  filter  and 
wash  with  10  per  cent,  solution  of  ammonium  sulphate. 
Then  dissolve  the  precipitate  on  the  filter  with  boiling  water 
made  slightly  alkaline  with  ammonia,  allow  the  solution 
to  cool,  and  make  up  the  volume  to  100  c.c.  by  the  addition 
of  water.  On  adding  15  c.c.  of  concentrated  sulphuric 
acid  the  temperature  should  rise  to  55°  to  60°  C.  This 
temperature  is  necessary  for  the  final  operation,  viz.  titra- 
tion with  standardised  potassium  permanganate  solution. 
Add  to  the  result  obtained  by  calculation  i  milligramme, 
to  allow  for  loss  due  to  the  solubility  of  ammonium  urate. 

Methods  of  Dimmock  and  Branson. — Dimmock  and 
Branson  ^-  have  recently  described  three  new  methods  for 

*  Lancet,  1907. 


122       GOUT  :    ETIOLOGY    AND    VARIETIES.  [Part  ii. 

the  determination  of  uric  acid  : — (a)  A  measuring  process, 
in  which  a  precipitate  of  ammonium  urate  is  measured  in 
a  tube  specially  shaped  and  graduated  in  parts  per  cent, 
of  uric  acid,  (b)  A  volumetric  process  in  which  a  precipi- 
tate of  ammonium  urate  is  collected  and  washed  with  a 
saturated  solution  of  ammonium  nitrate  until  free  from 
chlorides,  and  decomposed  after  solution  in  distilled  water 
by  adding  in  excess  a  known  amount  of  a  volumetric  solu- 
tion of  silver  nitrate.  After  filtering  off  and  washing  the 
precipitate  of  urate  of  silver,  the  amount  of  nitrate  of  silver 
in  the  filtrate  is  determined  by  means  of  a  standard  solu- 
tion of  thiocyanate  of  potassium,  the  filtrate  being  first 
rendered  acid  with  a  few  drops  of  dilute  nitric  acid  (i  in  3) ; 
a  few  drops  of  saturated  solution  of  iron  alum  are  used 
as  an  indicator,  (c)  A  gasometric  process,  in  which  the 
washed  ammonium  urate  is  decomposed  by  hypobromite  of 
sodium  in  a  specially  devised  apparatus  which  can  also  be 
used  for  the  determination  of  urea. 

Process  (a)  is  a  very  convenient  method,  and  gives 
approximately  correct  results  in  a  short  time.  Process 
(/;)  is  a  quick  method,  and  gives  very  concordant  results. 
Process  (c)  is  suitable  for  proportions  of  uric  acid  ranging 
from  I  in  1,000  to  i  in  5,000. 

General  preliminary  treatment  for  all  three  processes . 
— The  precipitate  used  in  the  three  foregoing  processes 
consists  of  ammonium  urate,  which  is  obtained  by  adding 
ammonium  chloride  or  ammonium  nitrate  to  urine  which 
has  previously  been  rendered  slightly  alkaline  by  the  addi- 
tion of  I  per  cent,  of  lithium  carbonate,  and  subsequently 
boiling,  the  precipitated  phosphates,  etc.,  being  removed 
by  filtration.  The  method  employed  is  as  follows  : — 
Take  100  c.c.  of  clear  urine  (warm  if  necessary  to  dissolve 
uric  acid  or  urates),  and  place  in  a  conical  flask  of  about 
400  c.c.  capacity,  add  i  gramme  of  lithium  carbonate, 
and  boil  the  whole  for  three  minutes.  If  frothing  occurs 
it  can  be  checked  by  blowing  on  the  upper  portion  of  the 


Gup.vn.]        ESTIMATION    OF    URIC    ACID.  123 

outside  of  the  flask.  Filter  the  liquid  whilst  hot,  and  wash 
the  precipitated  earthy  salts  with  a  little  distilled  water 
until  the  filtrate  measures   100  c.c. 

Process  [a). — To  50  c.c.  of  the  filtered  alkaline  urine, 
which  contains  the  uric  acid  as  lithium  urate,  add  5 
grammes  of  ammonium  chloride,  and  shake  the  flask  until 
solution  occurs.  After  three  minutes  warm  the  contents  of 
the  flask  to  50°  C.  so  as  to  secure  a  uniform  aggregation 
of  the  precipitated  urate  of  ammonium.  Now  pour  the 
whole  into  a  tube  graduated  in  parts  of  uric  acid  per 
100,  allow  deposition  to  take  place,  and  take  the  reading 
after  twenty-four  hours  have  elapsed.  If  the  urine  does 
not  contain  a  high  percentage  of  uric  acid  the  reading 
can  be  taken  in  four  hours.  If  any  ammonium  urate 
adheres  to  the  surface  of  the  glass  the  tube  should  be 
gently  rotated. 

Process  (6). — The  ammonium  urate  is  obtained  as  fol- 
lows : — To  50  c.c.  of  the  filtered  alkaline  urine  add  15 
grammes  of  ammonium  nitrate,  and  shake  the  flask  until  solu- 
tion occurs.  After  three  minutes  warm  the  contents  of  the 
flask  to  50°  C,  as  in  process  {a).  Transfer  the  whole  to  a 
beaker,  and  allow  to  stand  for  two  hours.  Collect  the  pre- 
cipitate on  a  filter  paper  of  5.5  centimetres  diameter,  and 
wash  with  about  10  c.c.  of  a  saturated  solution  of  ammonium 
nitrate  until  no  trace  of  chloride  is  indicated  by  the  addi- 
tion of  a  few  drops  of  a  solution  of  5  per  cent,  of  nitrate  of 
silver  acidulated  with  nitric  acid.  After  washing  the  pre- 
cipitate with  about  5  c.c.  of  distilled  water  to  remove 
excess  of  ammonium  nitrate,  transfer  it  with  the  filter  paper 
to  a  beaker  with  about  40  c.c.  of  hot  distilled  water  ;  solu- 
tion being  effected,  pour  off  from  the  filter  paper  and  wash 
the  latter  with  two  successive  quantities  of  5  c.c.  of 
distilled  water ;  to  the  50  c.c.  of  solution  thus  obtained 
a  measured  quantity  of  the  nitrate  of  silver  solution 
is  added — e.g.  10  c.c.  or  15  c.c.  Add  about  h  gramme 
of    powdered    talc,    and    stir    the   whole    well,    filter   into 


124       GOUT  :    ETIOLOGY    AND    VARIETIES,  [part  h. 

a  flask  previously  rinsed  with  a  little  distilled  water, 
and  wash  the  precipitate  with  about  lo  c.c.  of  dis- 
tilled water.  Add  to  the  filtrate  in  the  flask  a  few  drops 
of  dilute  nitric  acid  (i  in  3),  and  a  few  drops  of  a  saturated 
solution  of  iron  alum,  and  titrate  with  a  standard  solution  of 
thiocyanate  of  potassium.  The  number  of  cubic  centi- 
metres thus  obtained  is  subtracted  from  the  number  of  cubic 
centimetres  of  nitrate  of  silver  solution  originally  used, 
and  this  gives  the  exact  amount  of  nitrate  of  silver 
required  for  the  uric  acid  in  solution.     Solutions  required 

n 

for   this    process  : — Standard   silver    nitrate   solution :    — 

solution  silver  nitrate,  500  c.c.  ;  distilled  water,  20  c.c. 
One  c.c.  of  the  above  equals  uric  acid  0.005  gramme. 
Solution  of  potassium  thiocyanate  of  equivalent  strength 
to  above  ;   dilute  nitric  acid,  i  in  3. 

Process  (c). — Dissolve  31  grammes  of  ammonium  chloride 
in  100  c.c.  of  urine  previously  treated  with  lithium  car- 
bonate, decant  off  the  clear  portion,  and  transfer  the  re- 
mainder, with  the  precipitate,  to  a  narrow  cyhndrical  jar 
of  about  25  c.c.  capacity.  In  a  few  hours  the  precipitate 
will  be  ready  to  transfer  to  a  small  filter  paper,  5.5  centi- 
metres in  diameter.  Care  must  be  taken  that  any  precipi- 
tate adhering  to  the  vessels  used  is  detached  and  washed 
out  on  to  the  filter  paper  with  some  of  the  clear  urine. 
Wash  the  precipitate  and  edges  of  the  filter  paper  carefully 
with  distilled  water,  the  precipitate  being  disturbed  as 
little  as  possible,  so  that  the  wash  water  may  percolate 
through  it.  The  washing  of  the  precipitate  may  be  per- 
formed in  the  following  manner.  Allow  the  liquid  to  drain 
from  the  precipitate,  then  fill  the  filter  paper  with  distilled 
water  by  means  of  a  wash-bottle  with  a  fine  jet.  Repeat 
this  operation  a  second  and  a  third  time.  Test  some  of  the 
filtrate  with  a  5  per  cent,  solution  of  nitrate  of  silver,  acidu- 
lated with  nitric  acid  5  per  cent.  Only  a  very  shght  pre- 
cipitate  should  be  given,   indicating  the  absence  of  any 


Chap.  VII.]         ESTIMATION    OF    URIC    ACID.  125 

appreciable  amount  of  ammonium  chloride  ;  but  should 
the  filtrate  still  contain  this  salt,  wash  with  a  small  addi- 
tional amount  of  distilled  water.  Place  the  precipitate 
with  the  filter  paper  in  the  generating  bottle  of  apparatus, 
fill  the  tube  up  to  the  mark  (25  c.c.)  with  the  hypobromite 
solution,  and  lower  it  into  the  bottle  by  means  of  string. 
The  temperature  of  the  solution  should  approximate  to 
that  of  the  room  in  which  the  operations  are  carried  out. 
This  may  be  easily  attained  if  the  hypobromite  solution 
is  immersed  for  some  time  in  the  water  vessel  in  which  the 
generating  bottle  is  placed.  Now  place  the  cork  in  the 
generating  bottle,  and  plunge  the  bottle  in  a  vessel  of 
cold  water  of  a  similar  temperature  to  that  of  the  hypo- 
bromite solution.  After  two  minutes  adjust  the  water 
level  in  the  measuring  burette  to  zero,  and  then  close  the 
tap  and  observe  if  the  water  level  remains  constant.  In 
order  to  test  if  leakage  occurs  in  any  part  of  the  apparatus, 
alter  the  water  level  in  the  measuring  burette  ;  any  defect 
is  then  easily  seen.  Finally,  lift  the  generating  bottle  and 
allow  the  reagent  to  flow  out  of  the  tube,  and  shake  so  as  to 
promote  the  reaction  between  the  sodium  hypobromite  and 
the  ammonium  urate.  After  ten  minutes,  during  which 
time  the  bottle  should  be  shaken  at  intervals,  adjust  the 
level  in  the  two  tubes,  and  read  off  the  percentage  of  uric 
acid,  as  indicated  by  the  nitrogen  evolved.  The  hypo- 
bromite solution  is  prepared  as  follows  : — 

I  Caustic  soda,  41  grammes. 

I  Distilled    water  to   measure    100   c.c. 

/■  Bromine,  i  c.c. 
Bromine  solution  '  Potassium  bromide,  2  grammes. 
I  Distilled  water  to  measure  10  c.c. 

For  use  mix  equal  volumes  immediately  before  being 
required,  and  cool. 

Plumbism    and    gout. — Chronic    lead-poisoning  gives 


126       GOUT:    /ETIOLOGY    AND    VARIETIES.    [Part  ii. 

rise  to  both  chronic  kidney  disease  and  gout.  A  prolonged 
period  of  lead  intoxication  is,  as  a  rule,  required  to  pro- 
duce true  saturnine  gout. 

The  patient  suffering  from  saturnine  gout,  unlike  the 
majority  of  sufferers  from  inherited  gout,  is  pale,  thin,  and 
anaemic.  The  gouty  attacks  are  frequently  repeated,  and 
affect  many  joints,  whilst  signs  of  interstitial  nephritis 
make  their  appearance.  If  the  lead-poisoning  has  been 
of  short  duration  the  lesions  may  yield  to  treatment, 
but  after  a  prolonged  absorption  of  lead  into  the  system 
the  kidney  condition  is  generally  incurable. 

In  plumbism  bluish-black  discolorations  of  the  mucous 
membrane  of  the  intestine  occur.  These  patches,  on  micro- 
scopical examination,  exhibit  a  similar  condition  to  the 
mucous  membrane  of  the  gums  affected  with  the  lead  line. 
The  dark  deposits  are  on  the  surface  of  the  membrane,  and 
also  in  and  underneath  it.  They  are  not  specially  associated 
with  the  blood  vessels,  but  rather  with  the  lymphatics 
and  the  large  cells  of  the  mucous  membrane.  During  the 
attack  of  lead  colic  there  is  heightened  arterial  tension, 
which  is  the  cause  of  the  partial  suspension  of  the  renal 
function.  In  the  liver  a  fatty-granular  degeneration  of 
the  hepatic  cells  occurs,  together  with  an  intercellular 
cirrhosis.  In  the  kidneys  a  very  similar  change  takes 
place.  A  parenchymatous  nephritis  is  first  produced, 
and  this  runs  on  to  an  interstitial  nephritis. 

Sir  William  Roberts  *  considered  that  it  was  difficult  to 
believe  that  lead-poisoning  produces  the  same  constitu- 
tional diathesis  as  that  which  exists  in  true  gout,  and  pre- 
ferred to  think  that,  while  gout  and  plumbism  differ  in  all 
other  respects,  they  have  one  tendency  or  vice  in  common, 
namely  the  tendency  to  uratosis — that  is,  to  the  deposition 
of  sodium  biurate.  He  regarded  this  precipitation  as  a 
gouty  tendency  which  may  be  reinforced  by  lead-poison- 
ing, and  the  precipitation  in  connection  with  plumbism  as 

*  "  Transactions  of  the  Medical  Society,"  vol.  xiv.,  p.  88. 


CAP.vir.]  PLUMBISM    AND    GOUT.  127 

one  in  which  lead-poisoning  is  reinforced  by  a  previously 
existing  gouty  tendency. 

In  the  south  of  England  there  is  an  intimate  relation- 
ship between  gout  and  lead-poisoning  ;  but,  according  to 
the  observations  of  Thomas  Oliver,  this  relationship  does 
not  hold  good  in  the  north  of  England.  He  has  observed 
that  workmen  from  the  south  who  become  the  subjects  of 
lead-poisoning  develop  gout  in  the  north  of  England,  whilst 
the  natives  of  the  north,  though  equally  exposed,  seldom 
become  gouty,  even  when  the  kidneys  are  affected  by  the 
plumbism.  At  the  same  time  it  must  be  borne  in  mind 
that  gout,  as  a  disease,  is  not  met  with  in  the  north  with 
anything  like  the  frequency  that  it  is  in  the  south  of 
England.  This  has  been  ascribed  to  the  difference  in  the 
drinking  habits  of  the  people,  whisky  and  not  malt  liquor 
being  the  general  drink  in  the  north.  Oliver,  however, 
does  not  regard  this  as  a  complete  explanation,  but  con- 
siders that  in  some  way  or  other  the  result  is  due  to 
external  conditions  rather  than  to  the  use  of  beverages. 

Lorimer  *  arrived  at  the  following  facts  and  conclu- 
sions based  on  an  analysis  of  107  cases  of  gout  associated 
with  lead  impregnation  : — 

(i)  Age. — The  first  attack  of  gout  in  connection  with 
lead  impregnation  occurs  at  an  earlier  age  than  when 
independent  of  it. 

(2)  Hereditary  tendency.  —  In  gout  associated  with 
plumbism  the  influence  of  direct  hereditary  predisposition 
is  less  marked. 

(3)  Ancemia. — In  gout  the  blood  corpuscles  undergo 
no  change  in  number  and  quality,  but  in  gout  associated 
with  lead  impregnation  the  red  corpuscles  are  diminished 
in  number,  the  white  sometimes  increased,  and  the  red 
colouring  matter  is  reduced  in  amount. 

(4)  Asthenic  type  of  arthritis. — From  the  early  age  at 
which  saturnine  gout  occurs,  when  functional  activity  is 

*  Quarterly  Med.  Journ.,   1901. 


128       GOUT  :    .ETIOLOGY    AND    VARIETIES,  [part  ii. 

more  vigorous,  an  acute  and  asthenic  type  of  arthritis  might 
be  expected  to  prevail.  In  a  number  of  cases  in  the  first 
attack,  and  in  a  minority  of  cases  in  a  subsequent  attack, 
the  arthritis  assumes  this  type  ;  but  in  the  majority  of 
cases  the  type  of  arthritis  is  asthenic  and  the  accompany- 
ing pyrexia  sHght,  with  a  tendency  for  the  arthritis  to  pass 
insidiously  into  a  chronic  and  adynamic  form  ;  the  local 
and  constitutional  phenomena  are  less  intense,  but  more 
persistent,  lingering,  and  obstinate.  The  asthenic  type  of 
arthritis  appears  to  be  due  to  impaired  vitality,  to  the 
effects  of  lead  on  the  trophic  centres,  and  to  the  renal 
changes. 

(5)  The  aharticular  manifestations  of  gout  are  gener- 
ally less  marked  than  in  ordinary  gout,  renal  affection  in 
lead  gout,  however,  being  excepted. 

(6)  Arterial  thickening  and  degeneration. — A  sign  which 
was  observed  to  be  more  or  less  constantly  present,  and  in 
two-thirds  of  the  total  number  of  cases  pronouncedly 
marked,  was  an  arterio-capillary  fibrosis,  along  with  athero- 
matous changes,  the  result  of  the  combined  effects  of  gout 
and  plumbism,  leading  to  premature  senile  changes  in  the 
arterial  system.  The  combined  effect  of  the  two  toxic 
influences  is  to  increase  and  accentuate  arterial  degenera- 
tion and  induce  cardiac  hypertrophy,  which  is  generally 
present  as  the  disease  advances. 

(7)  Albuminuria. — Albuminuria  occurs  frequently  in 
lead-poisoning  ;  in  the  107  cases  it  was  present  in  89,  either 
as  an  intermittent  or  a  permanent  condition.  In  the  initial 
stages  it  may  be  absent,  or  be  intermittent  ;  in  subsequent 
stages  it  is  more  frequently  found,  either  as  an  occasional 
or  constant  occurrence  ;  but  in  the  later  stages  it  always 
exists  ;  so  that  it  may  be  affirmed  that  albuminuria  is  one 
of  the  most  constant,  certain,  and  characteristic  symptoms 
in  saturnine  gout,  and  is  always  present  at  some  time  in 
the  progress  of  the  disease. 

(8)  Frequency  of    chronic    interstitial    nephritis. — It   is, 


CAP.  VII.]  PLUMBISM    AND    GOUT.  129 

however,  when  the  combined  effects  of  gout  and  plumbism 
are  concentrated  on  the  kidney  that  the  distinguishing 
feature  of  most  serious  import  arises — namely,  chronic 
interstitial  nephritis.  Under  the  influence  of  lead,  there 
is  swelling,  degeneration,  and  shedding  of  the  renal  epi- 
thelium, glomerulitis,  thickening  of  the  vessels,  and  inter- 
stitial nephritis.  It  is  peculiar  to  the  gouty  kidney  that 
it  is  a  disease  of  advancing  years  ;  its  progress  is  slow, 
and  its  duration  long.  When,  however,  the  kidneys  are 
assailed  by  gout  and  lead,  the  onset  of  disease  is  accelerated 
and  the  duration  shortened. 


CHAPTER    VIII. 

IRREGULAR   GOUT. 

Irregular  gout  affecting  the  alimentary  tract — Irregular  gout 
affecting  the  air-passages  and  lungs — Irregular  gout  affecting 
the  heart  and  vessels — Irregular  gout  affecting  the  nervous 
system — Irregular  gout  affecting  the  genito-urinary  system 
— Irregular  gout  affecting  the  skin — Irregular  gout  affecting 
the  eye  and  ear — Other  irregular  gout  affections — Retrocedent 
or  metastatic  gout. 

Gout  appearing  in  any  situation  other  than  a  joint  is 
regarded  as  irregular  or  abarticular.  Different  forms  of 
regular  gout  may  accompany  arthritic  gout,  or  may  take 
its  place,  or  may  alternate  with  it.  Although  attacks  of  ir- 
regular gout  may  occur  in  persons  subject  to  articular  gout, 
yet  they  more  frequently  occur  in  those  who  have  never 
suffered  from  gout  in  the  joints,  but  who  are  predisposed  to 
gout  either  by  inheritance  or  by  their  mode  of  life.  Metas- 
tatic and  irregular  forms  of  gout  are  especially  apt  to  occur 
in  persons  of  poor  physique,  and  who  are  broken  down  in 
health. 

Undoubtedly  the  terms  "  irregular  gout  "  and  "  sup- 
pressed gout  "  have  frequently  been  applied  to  pathological 
conditions  in  no  way  connected  with  gout,  and  it  is  there- 
fore important  that  a  diagnosis  of  irregular  gout  should  be 
based  on  good  and  sufficient  grounds.  The  most  important 
points  to  pay  attention  to  in  the  diagnosis  of  irregular  gout 
are  the  question  of  heredity,  the  habits  of  the  patient,  the 
nature  of  the  attack,  a  careful  examination  of  the  urine, 
and,  if  possible,  of  the  blood  or  blood  serum,  and,  lastly, 
the  successful  reaction  to  therapeutic  remedies.     Cramps 

130 


Chap.  VIII.]  IRREGULAR    GOUT.  131 

and  aching  pains  in  various  muscles  and  tingling  sensations 
in  the  hands  and  feet  are  frequently  associated  with  irregu- 
lar gout. 

It  is  most  probable  that  the  symptoms  of  irregular 
gout  are  not  merely  dependent  on  the  local  deposit  of  minute 
crystals  of  sodium  biurate  in  the  affected  parts,  but  are 
rather  due  to  the  selective  action  of  a  soluble  toxin  in  the 
blood  on  a  naturally  weak  spot.  The  symptoms  vary 
with  the  age  and  constitution  of  each  subject,  but  in  every 
case  they  are  more  liable  to  develop  in  that  system  of  tissue 
which  happens  to  have,  from  natural  or  acquired  defects, 
the  weakest  nutritional  activity. 

The  various  forms  of  irregular  gout  may  be  conveniently 
classified  into  the  following  groups  : — (i)  Irregular  gout 
affecting  the  alimentary  tract  ;  (2)  irregular  gout  affecting 
the  air-passages  and  lungs  ;  (3)  irregular  gout  affecting  the 
heart  and  vessels ;  (4)  irregular  gout  affecting  the  nervous 
system ;  (5)  irregular  gout  affecting  the  genito-urinary 
system;  (6)  irregular  gout  affecting  the  skin;  (7)  irregular 
gout  affecting  the  eyes  and  ears  ;  (8)  other  irregular  gout 
affections. 

1.  Irregular  gout  affecting  the  alimentary  tract.— 
A  gouty  tonsillitis  is  occasionally  a  precursor  of  articular 
gout.  It  is  characterised  by  intense  congestion  and  oedema 
of  the  tonsils  and  soft  palate.  It  lasts  from  some  hours 
to  three  days,  but  always  subsides  on  the  appearance  of 
the  gout  in  the  joints. 

Acute  gouty  pharyngitis.  —  This  affection  is  charac- 
terised by  a  sudden  onset,  acute  course,  and  sudden  dis- 
appearance of  symptoms.  The  temperature  is  generally 
high,  and  the  local  pain  is  intense  and  out  of  proportion  to 
the  apparent  involvement  of  the  throat.  The  local  condi- 
tion consists  of  inflammation  of  the  pillars,  soft  palate, 
uvula,  and  posterior  wall  of  the  pharynx,  with  a  general 
red  cedematous  appearance,  and  a  tendency  for  the  inflam- 
mation to  descend  to  the  larynx.     The  mucous  membranes 


132        GOUT:    ETIOLOGY    AND    VARIETIES,  [part  ii. 

are  free  from  exudation,  and  the  glands  at  the  angle  of  the 
jaw  are  not  involved. 

Chronic  gouty  pharyngitis. —  A  chronic  pharyngitis  is  a 
fairly  common  form  of  irregular  gout,  and  is  also  occasion- 
ally associated  with  active  gout.  As  a  rule,  there  is  a 
general  irritation  and  congestion  of  the  whole  pharyngeal 
mucous  membrane,  with  a  tendency  to  lateral  thickening. 
There  may  be  some  secretion  of  tenacious  mucus,  but  not 
usually  to  any  marked  degree.  The  uvula  assumes  a  dusky- 
red  colour  and  is  oedematous. 

Gouty  parotitis  is  an  extremely  rare  form  of  irregular 
gout,  but  when  present  it  seriously  interferes  with  mastica- 
tion and  deglutition.  It  usually  develops  suddenly,  per- 
sists for  a  few  hours,  and  disappears.  Like  gouty  orchitis, 
it  readily  yields  to  treatment  with  colchicum,  and  also 
rapidly  subsides  on  the  appearance  of  regular  gout  in  one 
or  more  of  the  joints.  One  case  has  been  reported  in  which 
gouty  orchitis  occurred  during  an  attack  of  gouty  parotitis. 

Gouty  cesophagismus  occasionally  occurs,  and  may  be 
severe. 

A  sudden  gastralgia,  with  accompanying  derangement 
of  the  digestive  functions,  constitutes  an  occasional  form 
of  irregular  gout ;  it  may  alternate  with  a  true  arthritic 
attack,  or  with  urticaria,  or  eczema.  Acute  attacks  of 
enter algia  also  occur  in  gouty  subjects. 

Gouty  dyspepsia  is  a  very  common  form  of  irregular 
gout.  It  is  usually  accompanied  by  excessive  gastric 
acidity,  flatulence,  and  heartburn.  Gastric  pain,  dilata- 
tion of  the  stomach,  and  pyrosis  are  occasionally  associated 
with  this  form  of  dyspepsia,  which  is  frequently  of  a  pro- 
longed and  obstinate  nature.  In  other  cases  slight  attacks 
of  gastric  catarrh  occur  characterised  by  loss  of  appetite, 
furred  tongue,  foul  breath,  and  constipation. 

Hyperchlorhydria,  or  excessive  secretion  of  hydrochloric 
acid  in  the  gastric  juice,  occurs  in  some  gouty  subjects, 
and  in  such  should  be  regarded  as  a  form  of  irregular  gout. 


Chap. VIII.]  IRRECxULAR    GOUT.  133 

By  this,  I  do  not  mean  that  hyperchlorhydria  occurs  only 
in  gouty  subjects,  as  I  have  met  with  many  cases  of  it  in 
individuals  who  have  no  tendency  to  gout,  either  inherited 
or  acquired  ;  but  I  have  on  several  occasions  met  with  it 
in  gouty  people,  and  have  not  uncommonly  seen  it  alter- 
nate with  attacks  either  of  regular  gout  or  of  some  other 
form  of  irregular  gout.  The  gastric  discomfort  does  not 
begin  until  from  one  to  two  and  a  half  hours  after  a  meal, 
and  generally  continues  up  to  the  next  meal,  which  for 
a  time  relieves  it.  The  discomfort  may  simply  be  one  of 
distension  or  oppression,  or  may  amount  to  severe  pain, 
which  is  generally  described  as  being  of  a  burning  charac- 
ter. The  pain  is  usually  referred  to  the  epigastrium,  but 
may  also  be  felt  beneath  either  shoulder  blade.  The  condi- 
tion is  usually  accompanied  by  flatulent  distension,  acid 
eructations,  and  severe  heartburn.  The  eructations  give, 
for  the  time,  considerable  relief,  as  a  rule.  The  effect  of 
this  excessive  secretion  of  hydrochloric  acid  is  to  cause  a 
too  rapid  digestion  of  the  proteid  elements  of  the  food, 
with  retention  in  the  stomach  of  the  starchy  and  fatty 
constituents  of  the  food.  In  consequence  of  this  retention, 
the  gastric  secretion  is  kept  up,  while  at  the  same  time 
no  constituent  is  present  with  which  the  gastric  juice  can 
combine,  and,  in  consequence,  an  excessive  amount  of 
free  hydrochloric  acid  accumulates  in  the  stomach.  Un- 
doubtedly, some  gouty  subjects  have  the  habit  of  secreting 
an  excessive  amount  of  gastric  juice,  and  especially  does 
this  occur  as  a  consequence  of  the  consumption  of  a  diet 
too  rich  in  nitrogenous  substances. 

Gastro-intestinal  gout. — Attacks  of  gastro-intestinal  gout 
occasionally  alternate  with  attacks  of  articular  gout.  A 
patient  who  has  been  the  subject  of  articular  gout  may  be 
suddenly  seized  with  epigastric  pain,  nausea,  and  vomit- 
ing, which  recur  in  bouts.  The  vomiting  is  generally  re- 
peated in  each  attack  several  times,  and  the  attack  gener- 
ally lasts  from  three  to  five  hours.     At  other  times  there 


134       GOUT  :    ETIOLOGY    AND    VARIETIES,  ipart  ii. 

may  be  intestinal  crises,  in  the  form  of  diarrhoea,  lasting 
from  three  to  four  hours,  and  accompanied  by  colic  and 
sweating.  These  gastro-intestinal  attacks  are  accompanied 
by  a  marked  temporary  relief  to  the  joints. 

The  gastric  form  of  gout  manifests  itself  by  the  sudden 
occurrence  of  abdominal  pain,  not  necessarily  associated 
in  any  way  with  the  taking  of  food,  and  not  necessarily 
referred  to  any  particular  spot.  The  pain  may  be  very 
severe,  so  as  to  cause  more  or  less  collapse,  and  vomiting 
may  occur.  This  form  can  only  be  diagnosed  by  the 
absence  of  other  conditions  which  could  cause  the  pain, 
and  by  the  complete  and  immediate  disappearance  of 
the  pain  on  the  occurrence  of  an  acute  attack  of  regular 
gout. 

2.  Ipregfular  gout  affecting*  the  air-passag^es  and  lung-s. 
— Gouty  laryngitis.  —  Deposits  of  sodium  biurate  have 
been  found  in  the  vocal  cords,  the  arytenoids,  and  the 
crico-arytenoid  ligaments  and  joints.  Congestion  and 
swelling  of  the  mucous  membrane  occur,  and  the  conges- 
tion may  extend  to  the  vocal  cords.  The  principal  symp- 
toms are  hoarseness,  irritable  cough,  and  scanty  expectora- 
tion, which  is  occasionally  streaked  with  blood. 

Gouty  tracheitis. — This  affection  is  accompanied  by 
very   irritable   cough   and   scanty   expectoration. 

Acute  gouty  bronchitis  frequently  precedes  an  arthritic 
attack,  and  often  subsides  when  the  joints  become  affected. 
The  symptoms  of  acute  gouty  bronchitis  may  be  very 
severe,  and  the  heart's  action  often  becomes  irregular 
and  feeble.  The  expectoration  may  be  blood-stained, 
and  the  dyspnoea  is  frequently  severe. 

Chronic  gouty  bronchitis. — This  affection  is  accompanied 
by  an  irritable  cough  and  scanty  expectoration.  It  is 
especially  liable  to  alternate  with  arthritic  attacks. 

Gouty  asthma. — Attacks  may  alternate  with  arthritic 
attacks,  or  gouty  asthma  may  occur  in  early  life,  and 
articular  gout    may  develop  later,  or  gouty  asthma  may 


Chap.  VIII.]  IRREGULAR    GOUT.  135 

be  the  only  form  of  gout  inherited  from  a  parent  who 
was  the  subject  of  articular  gout. 

Gouty  pulmonary  congestion. — This  is  usually  at  the 
base  of  the  lungs,  but  occasionally  may  be  apical.  It  is 
accompanied  by  haemoptysis,  and  is  a  condition  that  may 
be  mistaken  for  phthisis. 

3.  Irregrular  grout  affecting"  the  heart  and  vessels.— 
Cardiac  disorders. — Paroxysmal  attacks  of  cardiac  irri- 
tability are  very  apt  to  occur  in  gout}^  subjects.  The 
attacks  are  nervous  in  origin,  and  are  evidenced  by  irregu- 
larity, tachycardia,  or  occasionally  bradycardia,  and  by 
dyspnoea  if  organic  disease  of  the  heart  exist. 

Alterations  in  the  cardiac  action,  from  the  influence 
of  the  toxic  agents  on  the  nervous  mechanism  of  the  heart, 
e.g.  arrhythmia,  tachycardia,  bradycardia,  angina,  frequently 
occur.  The  liability  to  these  disturbances  is  increased 
if  myocardial  degeneration  is  also  present. 

Sansom  *  states  that  he  has  observed  a  considerable 
number  of  cases  of  gout  and  gouty  manifestations  in  which 
there  has  been  a  course  of  severe  or  of  peculiar  and  per- 
plexing symptoms  after  an  attack  or  after  repeated  attacks 
of  influenza.  He  thinks  that  the  most  important  association 
of  the  post-influenzal  irregular  heart  is  with  gout  and 
goutiness.  In  many  cases  the  heart  symptoms — pain, 
distress,  and  heart  failure — have  been  very  severe,  and  in 
some  fatal. 

Mitchell  Bruce  accepts  as  evidence  of  the  gouty  nature 
of  a  cardiac  disorder  various  circumstances,  or  combinations 
of  circumstances,  which  may  be  stated  briefly  as  follows  : — 
(i)  a  personal  history  of  declared  gout,  present  or  pre- 
vious ;  (2)  a  personal  history  of  free  living,  and  usually 
of  hard  work,  with  occasional  explosions  suggestive  of 
irregular  gout,  in  the  form  of  haemorrhage  from  the  bowels, 
intestinal  fluxes,  sick  headaches,  irritability  of  the  bladder, 
eczema,   insomnia,   and   fits   of  irritability  or  depression  ; 

*  Lancet,  October,  1899. 


i3'6       GOUT  :    ETIOLOGY    AND    VARIETIES.  [Pa.t  n. 

(3)  relief  of  these  symptoms  by  treatment  directed  against 
gout — purgatives,  exercise,  spare  living,  and  various  alka- 
line salts  ;  and  (4)  a  family  history  of  gout,  megrim,  gravel, 
glycosuria,  asthma,  and  their  allies — well  marked,  direct, 
and  often  on  both  sides. 

The  first  evidence  of  gouty  trouble  in  connection  with 
the  heart  frequently  comes  on  after  exertion.  The  follow- 
ing is  the  description  given  by  Mitchell  Bruce  of  the  in- 
cidence of  such  an  attack.  The  patient  becomes  con- 
scious of  a  distressing  sensation  in  the  prsecordia — most 
likely  behind  the  middle  of  the  sternum.  This  is  pain, 
or  it  may  be  but  "  oppression,"  driving  him  to  unbutton 
his  vest,  or  to  unfasten  his  jersey,  which  seems  to  him 
to  gird  him  too  tightly.  If  the  attack  occur  during  exertion, 
he  has  to  pause,  looks  anxious,  and  clings  to  the  nearest 
support.  In  many  instances  the  paroxysm  is  anginal. 
There  may  be  no  palpitation,  unless  the  attack  has  come 
on  in  bed,  when  irregular  cardiac  action — "  fluttering  " — 
is  common.  In  either  case  the  mind  becomes  anxious. 
A  sense  of  weakness  or  faintness  pervades  the  chest  and 
head,  the  extremities  become  chiU,  and  a  cold  sweat  breaks 
out  on  the  surface  of  the  body.  Presently  abundant  flatu- 
lent eructations  occur ;  and  with  these  the  distressing 
sensations,  and  the  attack  as  a  whole,  pass  away. 

The  pain  complained  of  by  the  gouty  subject  appears 
to  be  essentially  cardiac.  When  fully  developed  it  occupies 
the  common  situations  of  the  pain  in  structural  disease 
of  the  heart,  particularly  such  as  involves  the  aortic  valves 
and  the  root  of  the  aorta.  It  is  referred  to  mid-sternum  ; 
or  it  is  a  "  tearing  sensation  at  the  heart."  In  other 
instances  it  is  not  a  pain  proper,  but  a  sense  of  oppression 
across  the  chest,  or  a  sense  of  tightness,  or  of  burning  like 
heartburn.  In  its  full  development  it  is  anginal,  and 
may  then  be  accompanied  by  a  variety  of  disturbances 
of  associated  parts,  as  we  have  already  described.  Pal- 
pitation occurs  in  different  forms  and  at  different  times 


Chap.  VIII.]  IRREGULAR    (iOUT.  137 

in  the  subjects  of  gouty  heart.  Palpitation  in  these  sub- 
jects may  be  readily  induced  by  indigestion,  and  as  readily 
relieved  by  eructation.  In  other  instances  of  the  gouty 
heart  it  is  entirely  absent.  Faintness  may  be  of  different 
degrees,  from  simple  "  giddiness  "  to  complete  syncope. 
Respiratory  disturbance  and  distress  are  prominent  features 
of  some  of  the  acute  attacks.  In  other  instances  the 
breathing  is  entirely  unaffected. 

In  a  patient  complaining  of  such  symptoms  physical 
examination  of  the  heart  generally  reveals  the  absence 
of  any  valvular  lesion.  Usually  there  are  present  a  feeble 
impulse,  ill-defined  limits  of  prsecordial  dulness,  feeble, 
dull  or  indefinite  sounds,  and  no  murmur.  This  indeter- 
minateness  of  the  results  of  physical  examination  may  be 
regarded  as  a  characteristic  of  the  gouty  heart.  The 
pulse  is  frequently  irregular,  sometimes  intermittent.  Often 
it  is  peculiarly  indefinite,  or  indeterminate,  like  the  prae- 
cordial  signs.  The  tension  is  either  moderate  or  actually 
low.     In  some  instances  the  wall  of  the  vessel  is  thickened. 

Anginal  and  pseudo-anginal  attacks.— These  attacks  may 
occur  either  in  connection  with  chronic  gout,  or  as  an 
occasional  manifestation  of  irregular  gout.  True  angina 
pectoris,  associated  with  widespread  arterial  degeneration 
and  softening  of  the  walls  of  the  heart,  occasionally  occurs 
in  gouty  subjects,  the  gouty  condition  no  doubt  being  a 
powerful  factor  in  the  production  of  the  degenerative 
changes  leading  up  to  the  anginal  attacks.  Pseudo-angina 
pectoris  unassociated  with  any  general  arterial  degeneration 
also  may  occur  in  the  gouty,  and  is  accompanied  by  severe 
pain  in  the  region  of  the  heart,  passing  down  the  left  arm, 
a  feeling  of  suffocation,  flatulency,  and  gastric  disturbance. 

The  toxic  agents  of  gout  acting  on  the  walls  of  the 
heart  may  set  up  chronic  myocarditis,  with  disease  of  the 
coronary  vessels.  Pericarditis  is  an  occasional  termination 
in  cases  where  the  gouty  form  of  Bright's  disease  is 
developed. 


138       GOUT  :    ETIOLOGY    AND    VARIETIES,  [part  ii. 

Gouty  phlebitis. — This  affection  is  a  fairly  common 
complication  of  chronic  gout,  but  it  may  also  be  a  phase 
of  irregular  gout.  It  may  occur  either  in  the  veins  of  a 
portion  of  a  limb  which  is  the  seat  of  gouty  inflammation, 
or  in  veins  quite  apart  from  the  presence  of  gouty  inflam- 
mation in  the  vicinity.  The  veins  of  the  lower  extremities 
are  most  commonly  affected,  especially  the  veins  of  the 
calf.  This  affection  is  not  uncommonly  of  prolonged 
duration,  and  is  very  apt  to  recur.  In  consequence  of  the 
thrombosis  that  ensues  great  care  must  be  exercised  to 
prevent  detachment  of  the  clot,  and  the  consequent  risk 
of  pulmonary  embolism.  The  oedema  of  the  limb  conse- 
quent on  the  thrombosis  generally  persists  for  some  time. 

When  the  deep  veins  of  the  calf  are  affected,  the  first 
symptom  is  frequently  a  sudden  and  acute  cramp-like 
pain,  which  is  soon  followed  by  deeply-seated  tenderness 
to  pressure.  There  is  a  tendency  to  frequent  recurrences 
of  the  attacks,  which  are  especially  prone  to  occur  when 
the  patient  is  fatigued  or  below  the  usual  standard  of 
health.  It  is  sometimes  the  only  manifestation  of  gouty 
inheritance,  but  is  frequently  combined  with  other  obviously 
gouty  symptoms. 

There  is  no  doubt  that  persons  of  gouty  habit  or  an- 
cestry are  more  than  commonly  liable  to  phlebitis,  and 
that  in  them  the  affection  usually  has  certain  distinguishing 
characters.  To  quote  Sir  James  Paget's  description  : 
"  Gouty  phlebitis  is  far  more  frequent  in  the  lower  limbs 
than  in  any  other  part  ;  but  it  is  not  limited  to  the  limb 
that  is,  or  has  been,  the  seat  of  ordinary  gout.  It  affects 
the  superficial  rather  than  the  deep  veins,  and  often  occurs 
in  patches,  affecting  (for  example)  on  one  day  a  short 
piece  of  a  saphenous  vein,  and  on  the  next  day  another 
piece  of  the  same  or  a  corresponding  piece  of  the  opposite 
vein,  or  of  a  femoral  vein.  It  shows  herein  an  evident 
disposition  towards  being  metastatic  and  symmetrical : 
characters  which,  I  may  remark  by  the  way,  are  strongly 


Chap.  VIII.]  IRRECxULAR    GOUT.  139 

in  favour  of  the  belief  that  the  essential  and  primary  dis- 
ease is  not  a  coagulation  of  the  blood,  but  an  inflammation 
of  portions  of  the  venous  wall." 

4.  Ippegular  g"out  affecting  the  nervous  system. — 
Migraine  and  neuralgia. — Attacks  of  migraine  and  of 
neuralgia  not  unfrequently  occur  in  persons  of  gouty  habits. 
Neuralgia  is  the  commonest  and  also  one  of  the  most 
troublesome  of  gouty  derangements.  The  fifth  nerve, 
posterior  tibial,  sciatic,  and  occipital  are  the  ones  most 
frequently  involved,  and  their  derangements  are  liable 
to  appear  and  disappear  suddenly,  or  take  the  place  of 
other  manifestations  of  the  disease. 

Neuritis. — Neuritis  is  by  no  means  infrequent,  and 
is  probably  most  encountered  in  the  third  and  fourth 
decades  of  life  ;  the  symptoms  are  numbness,  tingling, 
loss  of  power  in  the  affected  part,  muscular  wasting  occa- 
sionally, and  sometimes  very  severe  pain.  The  sciatic 
nerve  and  the  brachial  plexus  and  its  branches  are  most 
liable  to  this  form  of  neuritis.  The  affection  is  probably 
started  by  a  deposit  of  sodium  biurate  in  the  nerve-sheath 
setting  up  a  perineuritis,  with  subsequent  effusion  of 
lymph  within  the  sheath,  and  consequent  compression  of 
the  nerve  fibres.  When  this  occurs  in  the  sciatic  nerve 
it  is  the  cause  of  the  severe  and  prolonged  sciatica  that 
some  gouty  subjects  suffer  from.  In  sciatica  of  gouty 
origin  the  affection  is  not  always  confined  to  the  sciatic 
nerve  alone  ;  frequently  the  crural  nerve  is  simultaneously 
involved,  and  under  certain  circumstances  the  obturator 
nerve  is  also  affected. 

Apart  from  injury,  gout  is  undoubtedly  a  prominent 
setiological  factor  in  the  development  of  brachial  neuritis. 
The  neuritis  may  be  accompanied  by  any  of  the  ordinary 
manifestations  of  gout,  or  by  any  of  the  forms  of  irregular 
gout.  The  prominent  symptom  in  every  case  is  pain, 
sometimes  sudden  in  onset,  but  more  often  slight  and 
occasional  at  first  and  only  felt  on  making  certain  move- 


140        GOUT  :    ETIOLOGY    AND    VARIETIES,  ipart  il 

ments,  notably  those  of  raising  the  arm,  but  it  increases 
and  becomes  more  continuous  with  paroxysmal  exacer- 
bations. The  acute  forms  are  probably  in  most  cases 
at  the  outset  acute  inflammations  of  the  fibrous  structures 
of  the  muscles,  or  as  the  condition  is  aptly  termed  "  fibro- 
sitis."  The  mischief  spreads  from  the  muscles  to  the 
sheaths  of  the  nerves,  and  often  to  other  fibrous  structures 
in  the  vicinity,  and  when  the  acute  condition  subsides  a 
chronic  neuritis  is  often  left.  The  pain  is  often  very 
severe,  and  wasting  may  go  on  to  an  extreme  degree  ;  while, 
on  the  other  hand,  cases  occur  in  which  the  extent  of 
the  neuritis  is  very  limited  and  the  symptoms  are  slight. 
The  duration  is  seldom  less  than  three  or  four  months, 
and  may  extend  over  a  year  or  more.  The  older  the 
patient  the  more  chronic  the  case  is  likely  to  be,  while 
much  depends  on  the  degree  of  rest  which  the  parts  obtain. 

Insomnia  is  an  occasional  accompaniment  or  mani- 
festation of  irregular  gout.  This  condition  may  be  due 
to  the  ingestion  of  improper  food,  giving  rise  to  abnormal 
gastric  fermentation,  or  to  hepatic  derangement.  In  such 
cases  it  is  frequently  accompanied  by  heartburn  and 
palpitation. 

Mental  depression  is  frequently  associated  with  gouty 
attacks  affecting  the  liver,  and,  as  a  rule,  is  almost  imme- 
diately relieved  by  a  dose  of  blue  pill  at  night,  followed 
by  a  purge  of  Epsom  salts  in  the  morning. 

Attacks  of  vertigo  and  epilepsy  are  occasionally  asso- 
ciated with  the  gouty  state.  Gouty  inflammation  of  the 
meninges  of  the  spinal  cord  occasionally  occurs,  associated 
with  pain  and  tenderness  over  the  affected  area,  and  with 
pain  and  hyperassthesia  in  the  lower  extremities.  Three 
cases  of  transient  paraplegia  supposed  to  have  been  due 
to  gouty  congestion  of  the  spinal  cord  have  been  described. 

5.  Irregular  grout  affecting"  the  grenito-urinary  system. 
— Gouty  kidney. — It  is  possible  that  a  functional  affection 
of  the  kidneys  may  occur  in  connection  with  gout.      This 


Chap.  VIII.]  IRREGULAR    GOUT.  141 

functional  affection  may  subside  if  the  exciting  cause  of  it 
be  removed,  or  it  may  pass  on  to  a  structural  lesion,  which 
is  then  of  the  contracted  granular  type.  The  symptoms 
associated  with  the  gouty  kidney  so  produced  are  those 
usually  met  with  in  cases  of  contracted  granular  kidney. 
There  is  increased  frequency  of  micturition,  and  more 
than  the  normal  quantity  of  urine  is  passed.  The  urine 
may  or  may  not  contain  a  small  quantity  of  albumen. 
The  arterial  tension  is  increased,  and  this  constitutes  a 
point  of  great  importance  to  be  noticed,  since  cerebral 
haemorrhage,  hypertrophy  and  dilatation  of  the  heart, 
and  congestion  of  the  lungs  are  liable  to  supervene  on  this 
condition. 

Uric  acid  gravel  and  calculi. — These  deposits  frequently 
occur  in  early  life  among  those  with  a  gouty  inheritance, 
and  are  not  uncommonly  followed  later  in  life  by  true 
gouty  attacks.  The  presence  of  uratic  deposits  in  the 
kidney  may  produce  a  referred  pain  down  the  back  and 
sometimes  the  front  of  the  thigh.  This  pain  may  be 
sufficiently  severe  to  interfere  with  walking,  and  is  apt 
to  be  confounded  with  sciatica  or  rheumatism.  The  pain 
is  a  referred  one  and  is  dependent  on  the  irritation  pro- 
duced within  the  kidneys,  which  irritation  is  caused  by 
uratic  deposits,  or  by  the  passage  of  fine  uric  acid  gravel, 
or  occasionally  by  the  passage  of  an  excessive  amount  of 
uric  acid,  as  sometimes  occurs  in  cases  of  gouty  diabetes. 
A  careful  examination  of  the  urine  and  palpation  of 
the  kidneys  will  reveal  the  source  of  such  referred 
pains. 

Irritability  of  the  bladder  is  associated  with  the  passage 
of  scanty  urine  of  high  specific  gravity,  which  yields  a 
copious  deposit  of  amorphous  urates  on  cooling. 

Gouty  orchitis  and  epididymitis  are  rare  forms  of  irregular 
gout,  but  undoubtedly  these  affections  occasionally  occur 
quite  independently  of  any  urethral  infection.  The  gouty 
origin  is  frequently  shown  by  the  rapid  subsidence  of  the 


142        GOUT  :    ETIOLOGY    AND    VARIETIES.  [Part  ii. 

orchitis  and  epididymitis  if  an  attack  of  articular  gout 
supervenes,  and  also  by  the  successful  results  following 
treatment  with  colchicum. 

6.  Irreg-ulap  gout  affecting"  the  skin. — Gouty  sub- 
jects are  peculiarly  liable  to  certain  affections  of  the  skin, 
and  amongst  those  who  have  inherited  a  gouty  tendency 
the  skin  affections  may  constitute  the  only  manifestation 
of  gout.  The  following  are  the  skin  affections  liable  to 
be  associated  with  the  gouty  state. 

Eczema. — This  disease  of  the  skin  more  frequently 
occurs  in  association  with  gout  than  any  other.  It  often 
precedes  arthritic  gout,  and  may  even  occasionally  be  the 
sole  manifestation  of  gout.  It  may  assume  either  the 
acute  or  chronic  form,  and  generally  occurs  symmetrically 
on  both  sides  of  the  body.  It  is  most  prone  to  occur  in 
spring,  and  is  very  apt  to  recur.  Gouty  eczema  occurs 
most  frequently  in  the  following  situations,  viz.  the  external 
ear  and  around  it,  the  face  and  forehead,  the  back  of  the 
neck,  the  flexures  of  the  joints,  the  scrotum  and  prepuce, 
the  backs  of  the  hands  and  feet,  the  interdigital  surfaces, 
and  more  rarely  the  arms,  legs,  and  trunk. 

Some  authorities  have  doubted  whether  there  is  such 
a  disease  as  a  gouty  eczema  pure  and  simple,  but  it  is  a 
common  experience,  in  my  practice,  to  find  that  eczema 
is  very  prone  to  occur  among  the  gouty.  Among  the 
descendants  of  gouty  ancestors,  I  frequently  find  that 
certain  members  suffer  from  recurring  attacks  of  eczema, 
while  others  suffer  from  regular  gout.  Again,  with  some 
individuals  it  is  not  uncommon  to  find  attacks  of  eczema 
alternating  with  attacks  of  articular  gout,  or  to  find  that 
an  attack  of  eczema  subsides  with  almost  startling  rapidity 
when  an  attack  of  true  gout  supervenes,  or  vice  versd. 
It  is  true  that  it  is  impossible  to  diagnose  a  gouty  eczema 
at  sight,  but  a  careful  inquiry  into  the  patient's  history, 
and  into  the  family  history,  makes  the  diagnosis,  in  my 
opinion,  in  many  cases  a  certainty. 


Chap.  VIII.]  IRREGULAR    GOUT.  143 

Herpes  is  not  unfrequently  met  with  in  association 
with  gout. 

Pruritus  and  prurigo  occasionally  occur  in  gouty  sub- 
jects, especially  in  connection  with  gouty  glycosuria. 
Pruritus  is  generally  localised,  and  especially  affects  the 
arms  and  the  vulva  ;    occasionally  it  is  general. 

Urticaria  sometimes  occurs  as  a  result  of  the  gouty 
state. 

For  a  long  time,  and  by  many  authorities  in  this  country, 
psoriasis  has  been  regarded  as  to  a  great  extent  a  mani- 
festation of  the  "  gouty  diathesis."  My  experience,  how- 
ever, is  that  psoriasis  is  not  met  with  more  frequently 
among  gouty  individuals  than  among  the  non-gouty,  and 
I  am  strongly  of  opinion  that  no  such  entity  as  a  gouty 
psoriasis  exists. 

Pospeloff  has  observed  a  macular  form  of  gouty  skin 
eruption.  The  latter  can  be  seen  in  three  different  stages. 
The  first  stage  consists  of  disseminated,  rusty  brown, 
irregular  or  dendroid  spots,  which  do  not  disappear  on 
pressure  and  are  seen  chiefly  on  the  shins.  Under  suit- 
able treatment,  and  often  without  it,  these  spots  disappear, 
but  are  observed  again  with  each  fresh  attack  of  gout. 
If  the  original  disease  persists,  owing  to  the  patient's 
habits,  the  second  stage  of  the  eruption  occurs,  which 
consists  of  bluish-violet  spots  in  addition  to  those  of  a 
rusty  brown  colour.  The  spots  do  not  disappear  on  pres- 
sure with  the  finger,  thus  indicating  an  effusion  of  blood 
into  the  skin  and  cellular  tissue.  As  the  blood  collects 
under  the  horny  layer  of  the  epidermis  the  latter  gets  soaked 
and  separated,  and  forms  a  series  of  large  scales  with  tooth- 
like margins  of  the  macerated  white  horny  layer.  A  micro- 
scopical examination  of  an  excised  piece  of  skin  by  direct 
and  by  polarised  light  shows  that  the  violet-coloured  and 
rusty  red  spots  are  due  not  only  to  a  deposit  in  the  corium 
of  blood  pigment,  but  also  of  sodium  biurate  and  of  crystals 
of   uric  acid.     If   the  gout   increases  a  general  erythema 


144       GOUT:    ETIOLOGY    AND    VARIETIES,  [part  ii. 

of  the  affected  limb  occurs  ;  the  reddened  skin  becomes 
shiny,  sloughs  in  places,  and  ulcers  are  formed  ;  this  con- 
stitutes the  third  stage  of  these  gouty  skin  lesions. 

7.  Irregular  grout  affecting"  the  eye  and  ear.— 
Gout  certainly  plays  an  important  part  in  eye  affections, 
although  in  only  a  few  cases  have  definite  deposits  of 
sodium  biurate  been  found  in  the  conjunctiva  or  elsewhere. 
Conjunctivitis,  episcleritis,  sclerotitis,  iritis,  and  irido- 
cyclitis are  the  most  common  forms  of  gouty  eye  affections, 
and  they  are  all  extremely  liable  to  recur.  Gouty  sub- 
jects are  more  prone  than  others  to  suffer  from  glaucoma, 
and  cases  of  hsemorrhagic  retinitis  and  optic  neuritis  of 
gouty  origin  have  been  described. 

Gout  may  be  a  cause  of  ear  diseases,  especially  in  causing 
earache  at  night  and  tinnitus  aurium.  Mirk  has  recorded 
deposits  in  the  tympanic  membrane,  and  he  is  of  opinion 
that  some  cases  with  subjective  noises  are  due  to  gouty 
deposits  in  the  labyrinth.  Gout  is  also  said  to  exercise 
considerable  influence  in  the  development  of  exostoses 
in  the  external  auditory  canal.  Occasionally  a  gouty 
neuritis  affecting  the  terminations  of  the  auditory  nerve 
causes  deafness. 

8.  Other  irregular  gout  affections. — Glycosuria  and 
diabetes. — The  development  of  glycosuria  or  diabetes  in 
persons  of  gouty  ancestry  is  undoubted.  The  glycosuria 
is  in  all  probability  frequently  hepatic  in  its  origin. 
Glycosuria  is  generally  associated  with  some  form  of 
irregular  gout,  and  but  seldom  with  the  ordinary  articular 
gout,  but  very  occasionally  it  alternates  with  true 
gouty  attacks,  and  then,  while  the  glycosuria  lasts,  the 
patient  is  quite  free  from  articular  gout,  and  vice  versa. 
The  glycosuria  may  at  first  be  very  slight,  but  if  not  checked 
by  proper  dietetic  treatment  it  may  lapse  into  true  diabetes. 
With  regard  to  the  prognosis  in  gouty  diabetes,  much 
depends  on  the  manner  in  which  the  affection  responds 
to  dietetic  treatment.     If  the  sugar  in  the  urine  quickly 


chap.vui.,  irregular    gout.  145 

disappear,  and  if  several  months  elapse  before  its  reappear- 
ance, then  the  prognosis  is  fairly  good,  and  life  may  con- 
tinue for  many  years. 

Hepatic  congestion. — A  condition  of  congestion  of  the 
liver,  or  possibly  of  subacute  parenchymatous  hepatitis, 
popularly  known  as  "  gout  in  the  liver,"  is  occasionally 
met  with  in  gouty  subjects,  or  in  those  who  have  inherited 
a  gouty  tendency. 

Pains  in  the  head,  chest,  abdomen,  joints,  and  other 
parts,  lasting  for  a  few  minutes  to  some  hours  or  even 
two  or  three  days,  are  frequently  gouty  in  origin.  At  times 
it  is  difficult  to  recognise  them  as  forms  of  irregular  gout, 
but  a  careful  inquiry  into  the  family  history  and  the  habits 
of  the  patient  will  often  settle  the  question.  Such  pains 
occurring  in  one  who  inherits  from  his  family  a  gouty 
tendency,  or  who  eats  and  drinks  too  much,  and  at  the 
same  time  takes  too  little  exercise,  are  generally  indicative 
of  a  gouty  origin. 

During  the  past  few  years  I  have  noticed  in  several 
cases  of  so-called  "  hay-fever  "  a  gouty  tendency  under- 
lying the  local  affection.  Such  cases  resisted  cure  until, 
in  addition  to  local  treatment,  attention  was  paid  to  the 
gouty  condition,  especially  with  regard  to  the  dietary. 
These  observations  confirm  those  of  Karl  Grube,  who 
states  that  in  all  cases  which  were  treated  successfully 
by  him  such  gouty  tendency  could  be  traced  to  be  under- 
lying the  local  affection.  He  also  points  out  the  fact 
that  hay-fever,  like  gout,  is  more  common  in  England 
than  in  any  other  country.  Sir  Dyce  Duckworth,  too,  has 
also  noticed  the  connection  between  gout  and  hay-fever. 

Retrocedent  or  metastatic  gout. — This  form  of  gout  occurs 
when  a  sudden  subsidence  of  the  inflammation  in  a  gouty 
joint  is  succeeded  by  the  development  of  the  disease  in 
one  or  more  of  the  internal  viscera,  such  as  the  stomach, 
intestines,  heart,  or  liver.  Persons  subject  to  retrocedent 
gout  are  generally  in  a  debilitated  condition,  and  of  feeble 


146       GOUT:    .ETIOLOGY    AND    VARIETIES.    [Part  ii. 

constitution.  The  attacks  frequently  follow  an  exposure 
to  cold  while  suffering  from  an  articular  attack,  and  especially 
after  indiscretion  in  diet.  Attacks  of  retrocedent  gout 
have  also  not  uncommonly  followed  the  extremely  baneful 
practice  of  suddenly  plunging  a  gouty  foot  into  cold  water. 
If  the  attacks  rapidly  shift  their  position  the  affection  is 
termed  flying  gout.  It  is  quite  possible  that  attacks  of 
retrocedent  gout  are  caused  by  a  deposition  of  the  crystalline 
sodium  biurate  in  the  affected  viscus,  and  that  this  crystal- 
line biurate  acts  as  a  mechanical  irritant,  and  so  produces 
inflammation  of  the  organ.  On  the  other  hand,  these 
attacks  may  simply  be  of  nervous  reflex  origin,  due  to 
vaso-motor  disturbance  producing  a  condition  of  hyper- 
aemia  or  congestion  of  the  affected  viscus.  The  following 
are  the  principal  forms  of  retrocedent  gout,  with  the  symp- 
toms indicative  of  the  sudden  transference  of  the  attack 
to  the  affected  viscus. 

Retrocedent  gout  of  the  stomach. — The  symptoms  are 
severe  pain  in  the  stomach,  accompanied  usually  by  vomit- 
ing and  a  feeling  of  general  oppression,  depression,  and 
faintness.     Palpitation  may  occur. 

Retrocedent  gout  of  the  intestines. — The  usual  symptoms 
are  severe  abdominal  pain,  vomiting,  tympanites,  and 
constipation. 

Retrocedent  gout  of  the  heart. — The  symptoms  are  severe 
palpitation,  pain  in  the  region  of  the  heart,  a  sensation 
of  constriction  of  the  chest,  dyspnoea,  a  small  feeble  pulse, 
and  great  anxiety.     Syncopal  attacks  may  occur. 

Retrocedent  gout  of  the  brain. — Apoplexy  is  the  most 
frequent  symptom.  Congestion  of  the  brain  or  meninges 
may  occur,  and  may  be  followed  by  headache,  stupor, 
convulsions,  delirium,  and  occasionally  by  maniacal  attacks. 
Transient  attacks  of  aphasia,  amnesia,  and  hemiplegia  some- 
times occur,  and  are  probably  due  to  congestion  of  the  brain. 

Gouty  orchitis  and  -parotitis  of  metastatic  origin  have 
occasionally  been  known  to  occur. 


CHAPTER    IX. 
DIFFERENTIAL   DIAGNOSIS. 

Differential  diagnosis  of  chronic  diseases  of  the  joints — Forms 
of  rheumatoid  arthritis — Distinction  of  gout  from  rheumatoid 
arthritis — Distinction  of  gout  from  rheumatism — Distinction 
of  gout  from  various  diseases  of  the  joints — Prognosis  in 
gout. 

Differential  diagnosis  of  chronic  diseases  of  the  joints. 

— The  recognition  of  acute  gout  is  a  very  easy  matter, 
but  the  distinction  of  chronic  gout  from  other  chronic 
diseases  of  the  joints  is  often  a  matter  of  considerable 
difficulty ;  a  difficulty  which  is  not  diminished  by  the 
general  desire  on  the  part  of  our  patients  to  have  a  dis- 
ease labelled  with  some  distinctive  title.  There  is  much 
looseness  in  the  diagnosis,  and  consequently  in  the  treat- 
ment, of  joint  affections,  due  to  a  great  extent  to  the  descrip- 
tions of  joint  diseases  in  text-books  not  being  up  to  date 
with  the  advances  of  scientific  knowledge  as  to  their  mode 
of  origin  and  pathology.  Perhaps  the  best  classification 
of  joint  diseases  is  that  of  Bannatyne,  who  divides  them 
into  three  great  classes  : — (i)  the  bacterial  or  toxic  arthro- 
pathies ;  (2)  the  nerve  arthropathies  ;  and  (3)  the  senile 
degenerative  arthropathies.  To  this  division  I  would  add 
a  fourth  class — viz.  those  due  to  interference  with  the 
nutrition  of  the  joints  by  circulatory  changes,  such  as 
occur  in  Raynaud's  disease.  The  term  toxic  is  not  meant 
to  be  confined  to  the  products  of  bacterial  activity  only, 
but  includes  those  arising  from  the  tissues  themselves, 
or  by  chemical  processes,  such  as  the  toxic  substance  or 
substances  causing  gout. 

147 


148       GOUT  :    ETIOLOGY    AND    VARIETIES.  [Part  ii. 

Another  classification  of  arthritic  cases  is  into  (i)  the 
essential  arthropathies — i.e.  those  in  which  the  joint  troubles 
form  the  principal  or  prominent  sj^mptom  of  the  disease, 
such  as  gout,  rheumatism,  rheumatoid  arthritis,  and  senile 
arthritis  ;  and  (2)  the  accidental  arthropathies  — i.e.  those 
which,  although  they  may  occur  in  the  course  of  a  disease, 
yet  are  not  essential  symptoms  of  that  disease,  such  as 
gonorrhoeal,  scarlatinal,  malarial,  tuberculous,  syphilitic, 
pneumococcic,   and  nerve   arthropathies. 

With  regard  to  the  bacterial  arthropathies,  considerable 
discussion  has  arisen  as  to  whether  the  bacteria  or  their 
products  are  the  cause  of  the  symptoms.  I  think  that  the 
balance  of  evidence  is  strongly  in  favour  of  the  joint  troubles 
being  due  to  the  micro-organisms  themselves,  since  the 
micro-organisms  of  rheumatism,  gonorrhoea,  pneumonia, 
and  possibly  rheumatoid  arthritis,  have  been  found  in  the 
joint  structures  and  joint  fluids.  Moreover,  in  those  cases 
where  operative  treatment  of  the  joints  has  been  resorted 
to,  the  rapid  subsidence  of  the  symptoms  points  to  the 
joints  being  the  seat  of  bacterial  infection,  rather  than  to 
their  being  affected  by  toxic  products  elaborated  elsewhere. 
Certainly  it  may  be  accepted  that  infection  plays  a  most 
important  part  in  the  production  of  joint  diseases,  while  a 
general  defect  of  nutrition  underlies  many,  if  not  all,  of 
the  chronic  forms  of  arthritis.  Unfortunately,  the  term 
rheumatism  has  been  applied  with  too  much  looseness  and 
too  generally.  Now  that  it  is  known  that  acute  rheumatism 
is  itself  an  infective  disease,  it  is  recognised  that  many 
cases  of  arthritis  which  have  been  termed  rheumatism 
certainly  belong  to  the  infective  class. 

I  propose  first  to  consider  the  differential  diagnosis 
of  the  three  forms  of  chronic  joint  disease  that  are  most 
frequently  met  with,  that  are  most  apt  to  be  confounded, 
and  that  therefore  offer  the  principal  difficulties  in  diagnosis 
— viz.  gout,  rheumatoid  arthritis,  and  rheumatism.  The 
differential  diagnosis  of  these  diseases  is  a  very  important 


Chap.  IX.]  RHEUMATOID    ARTHRITIS.  149 

matter,  and  it  is  all  the  more  important  to  direct  attention 
to  such  diagnosis,  because  undoubtedly  in  the  past  many 
cases  of  rheumatoid  arthritis  have  escaped  recognition, 
and  have  been'  diagnosed  either  as  rheumatism  or  as  gout. 
When  it  is  considered  that  tlie  treatment  of  these  three 
diseases  is  quite  different,  the  necessity  for  a  correct  diag- 
nosis is  manifest.  It  is  probable  that  many  cases  which 
are  diagnosed  as  chronic  rheumatism  of  the  joints  are  not 
chronic  rheumatism  at  all  ;  many  of  them  are  cases  of 
rheumatoid  arthritis,  and  a  fair  number  are  cases  of  gout. 
I  believe  chronic  rheumatism  of  the  joints — chronic  arthritic 
rheumatism — to  be  a  comparatively  rare  affection  ;  at 
any  rate,  it  is  not  very  frequently  met  with.  Cases  are 
frequently  diagnosed  as  cases  of  chronic  rheumatism,  in 
which  there  are  great  deformities  of  the  joints,  lipping  of 
the  cartilages,  osteophytic  outgrowths,  and  grating  of 
the  ends  of  the  bones.  Those  are  cases  of  rheumatoid 
arthritis.  In  chronic  rheumatism,  neither  lipping  of  the 
cartilages  nor  the  osteophytic  outgrowths  which  are  so 
diagnostic  of  rheumatoid  arthritis  ever  occur. 

Rheumatoid  arthritis — The  term  "rheumatoid  ar- 
thritis "  is  objectionable,  as  suggesting  a  causal  con- 
nection with  rheumatism.  If,  however,  it  is  employed  and 
understood  as  merely  meaning  an  arthritis  somewhat 
resembling  some  forms  of  rheumatism,  the  term  may  be 
retained,  although  the  name  "arthritis  deformans"  is 
less  open  to  objection.  I  propose,  however,  to  retain  the 
term  "  rheumatoid  arthritis,"  owing  to  its  long  usage, 
as  I  am  afraid  that  the  description  of  that  disease  under 
another  and  less  recognised  name  may  lead  to  confusion. 
By  rheumatoid  arthritis  I  mean  the  disease  known  as  "  arth- 
ritis deformans,"  or  "  polyarthritis  deformans,"  or  "  rheu- 
matic gout."  I  think  that  very  often  the  unfortunate 
name  of  "  rheumatic  gout,"  as  applied  to  rheumatoid 
arthritis,  is  a  cause  of  the  two  conditions  being  confused. 
Certainly  it  is  a  name  which  covers  a  multitude  of  sins 


150        GOUT:    ETIOLOGY    AND    VARIETIES,  [part  ii. 

and  errors  in  diagnosis,  and  it  is  a  term  which  ought  to 
be  abandoned. 

The    cases    hitherto    grouped    together    as    rheumatoid 
arthritis  undoubtedly  include  more  than   one  disease.     I 
should  define   true  rheumatoid  arthritis  as  a  progressive 
degeneration   of   the  joints,   consisting  of   changes  in   the 
synovial  membranes,   cartilages,   and  bones,   accompanied 
by   atrophy   of   some   structures   and   by   hypertrophy   of 
others.     In  chronic  cases  marked  osteophytic  outgrowths 
are  peculiar  to  this  disease.     Heberden,    in  1804,  was  one 
of  the  first  to  distinguish  between  this  disease  and  rheu- 
matism.     He    pointed    out    that    there    was    swelling    of 
the  affected  joint,  but  little  or  no  fever,  no  great  pain, 
and  no  redness  of  the  skin  ;    that  the  disease  generally 
attacked  joint  after  joint,  and  that  it  was  very  crippling  ; 
that  the  fingers  and  wrists  were  especially  liable  to  the 
disease,   and  that   the   terminal  phalangeal  joints   of   the 
fingers    were    liable    to    become    affected    with    nodosities, 
which  have  since  become  known  as    "  Heberden's  nodes." 
The   disease    occurs   in    acute,    subacute,    and   chronic 
forms.     The  chronic  form  may  be  chronic  from  the  first, 
or  may  be  secondary  to  an  acute  or  subacute  attack.     The 
acute  and  subacute  forms  are  characterised  by  inflammatory 
changes   in   the   affected   joints,   by   erosion   of   cartilages 
and  bones,  by  nerve  and  trophic  phenomena,  and  by  glan- 
dular enlargement.     It  is  polyarticular,   and  in  its  acute 
and  subacute  forms  occurs  especially  in  children  and  young 
adults.     The    disease    usually    commences    in    one    joint, 
commonly  one   of   the  metacarpo-phalangeal  articulations, 
and  then  rapidly  spreads  to  most  of  the  other  joints.    The 
symmetrical  nature  of  the  affection  is  usually  well  marked, 
and  the  joints   are  painful,   hot,   and  present  a  spindle- 
shaped  enlargement,   but  no   outgrowth  or  thickening  of 
either    cartilage    or    bone    during    the    acute    stage.     The 
chronic  forms  are  characterised  by  progressive  thickening 
and  hardening  of  all  the  joint  structures,  by  the  formation 


Chap.  IX.  RHEUMATOID    ARTHRITIS.       .  151 

of  osteophytes,  by  the  lipping  of  cartilages,  and  by  the 
development  of  deformities.  The  disease  may  affect 
several  joints,  or  be  confined  to  one  or  two.  It  most 
commonly  occurs  in  middle  life,  and  in  females.  Com- 
paratively slight  injuries  of  a  joint,  especially  of  a  small 
joint,  may  lead  to  rheumatoid  arthritis,  and  to  an 
extension  of  the  process  to  other  joints  in  a  symmetrical 
order.  The  injuries  are  frequently  the  outcome  of  exces- 
sive work  and  strain,  especially  in  elderly  and  enfeebled 
persons  with  a  diminished  power  of  resistance,  increasing 
with  years  and  with  imperfect  nutrition. 

The  three  divisions  of  the  disease  proposed  by  Charcot 
constitute  the  generally  adopted  classification  of  the  forms 
of  rheumatoid  arthritis  for  a  study  of  their  symptoms. 
They  are  (i)  cases  with  Heberden's  nodes  ;  (2)  the  general 
progressive  form  ;  and  (3)  the  partial  or  monarticular 
form.  This  last-mentioned  monarticular  form  is,  however, 
in  my  opinion,  an  absolutely  distinct  disease  from  rheuma- 
toid arthritis,  and  I  shall  describe  it  later  among  the  senile 
arthropathies. 

I.  Cases  with  Heberden's  nodes. — These  cases  represent 
the  mildest  degree  of  the  disease.  The  nodes  consist  of 
httle  hard  swellings  of  the  finger  joints,  affecting  almost 
entirely  the  terminal  phalangeal,  and  are  due  to  a  very 
chronic  form  of  rheumatoid  arthritis.  This  type  is  more 
commonly  met  with  in  women  than  in  men,  and  usually 
at  or  after  the  middle  period  of  life.  The  nodules  are 
due  to  enlargement  of  the  ends  of  the  bones,  which  are 
frequently  covered  by  a  pouch  of  the  projecting  synovial 
membrane,  which  acts  somewhat  as  a  bursa.  The  joints 
become  swollen  and  tender.  The  cartilages  are  softened, 
and  the  ends  of  the  bones  are  eburnated.  The  enlarge- 
ments are  osseous  in  character,  but  there  may  be  a 
certain  amount  of  increase  of  the  periarticular  fibrous 
tissues.  After  a  time  the  disease  usually  becomes  arrested, 
but  the  swelHngs  remain,   and  eventually  may  cause  no 


153        GOUT  :    ETIOLOGY    AND    VARIETIES,  [part  ii. 

discomfort.  Treatment  cannot  produce  any  diminution 
in  size  of  the  bony  growths,  but  may  effect  a  decrease  in 
size  of  the  periarticular  tissues  referred  to. 

Heberden's  nodes  are  frequently  associated  with  some 
uterine  disturbance.  Heberden,  in  his  original  paper, 
particularly  noted  the  fact  that  the  thirty-three  cases 
he  described  occurred  only  in  women,  and  in  women  of 
middle  age.  This  form  of  rheumatoid  artliritis  touches  a 
point  of  age  beyond  which  the  influence  of  the  sexual 
system  is  likely  to  be  much  diminished,  and  there  is  un- 
doubtedly a  direct  connection  between  it  and  uterine 
troubles  associated  with  the  climacteric.  The  affection  is 
not  commonly  very  progressive,  and  never  reaches  to 
much  deformity  ;  but,  on  the  other  hand,  there  is  no 
.retrocession  of  the  chronic  arthritis.  The  uterine  troubles 
and  the  active  affection  of  the  joints  subside  together. 

Apart  from  Heberden's  nodes,  other  forms  of  chronic 
arthritis  are  frequently  associated  with  and  determined 
by  uterine  and  ovarian  troubles.  It  has  for  some  time 
been  held  that  the  joint  troubles  are  due  to  reflex  trophic 
influence,  the  excessive  uterine  irritation  being  reflected 
from  the  spinal  cord  to  the  joints  ;  but  I  cannot  help 
thinking  that  a  more  probable  explanation  is  that  the 
diseased  uterus  becomes  the  channel  by  which  an  infective 
or  septic  arthritis,  generally  leucorrhoeal  in  origin,  is  started 
in  the  joints.  In  a  similar  way  a  chronic  urethral  and 
prostatic  affection  in  men,  quite  apart  from  gonorrhoea, 
may  give  rise  to  a  chronic  arthritis  ;  such  an  arthritis  may 
also  be  started  by  the  use  of  an  imperfectly  clean  catheter. 
I  have  had  under  me  in  the  course  of  the  past  twelve  years 
six  cases  of  severe  chronic  arthritis,  indistinguishable  from 
rheumatoid  arthritis,  in  which  the  disease  followed  the 
removal  of  both  ovaries.  Whether  in  these  cases  the 
disease  occurred  in  consequence  of  the  removal  of  the 
ovaries,  or  in  association  with  the  diseases  requiring 
their  removal,  I  am  unable  to  say. 


Chap.  IX.]  RHEUMATOID    ARTHRITIS.  153 

2.  The  general  progressive  form.  —  Of  this  there  are 
two  varieties — the  acute  and  the  chronic.  The  acute  form 
has  been  previously  referred  to.  It  may  resemble,  and 
certainly  has  been  mistaken  for,  acute  articular  rheumatism. 
It  generally  starts  in  one  joint,  and  subsequently  involves 
many.  There  is  not  much  redness  of  the  affected  joints, 
and  only  moderate  fever.  It  is  most  common  in  young 
adults  and  young  women.  Among  the  last-mentioned  it 
is  often  connected  with  recent  delivery,  rapid  child-bearing, 
or  excessive  lactation.  Rheumatoid  arthritis  certainly 
occurs  in  children,  but  very  rarely,  and  even  more  rarely 
than  the  joint  disease  described  by  Still,  to  which  refer- 
ence will  presently  be  made. 

The  chronic  form  is  much  commoner  than  the  acute. 
The  joints  that  have  been  most  especially  and  actively 
used,  according  to  the  former  occupation  or  employment 
of  the  patient,  are  those  which  usually  show  the  first  signs 
of  the  disease.  The  affection  commences  with  slight 
swelling  and  pain  on  movement.  The  amount  of  effusion 
into  the  joint  is  variable,  and  may  be  marked  or  slight. 
The  hands  and  feet,  especially  the  hands,  are  most  liable 
to  be  first  affected,  and  the  disease  then  tends  to  advance 
more  or  less  up  the  limbs  towards  the  trunk,  obeying,  as 
Charcot  described,  "  the  centripetal  law."  In  extreme 
cases  every  joint  in  the  body  may  be  affected.  The  tem- 
poro-maxillary  articulation  becomes  the  seat  of  rheumatoid 
arthritis  in  about  25  per  cent,  of  the  total  number  of  cases. 

At  a  later  period  the  articulations  of  the  spine  may 
become  involved.  The  disease  usually  attacks  the  cervical 
vertebrae  first,  causing  pain  at  the  back  of  the  neck,  and 
rendering  flexion  of  the  neck  and  rotation  of  the  head 
difficult.  The  dorsal  and  lumbar  vertebrae  may  be  next 
affected,  so  that  in  bad  cases  the  spine  may  be  converted 
into  a  rigid  column.  Pain  may  be  very  severe,  especially 
at  night  ;  while,  on  the  other  hand,  the  case  may  proceed 
to  extreme  deformity  without  pain. 


154        GOUT:    ETIOLOGY    AND    VARIETIES,  [part  n. 

Very  considerable  alterations  in  the  shape  of  the  joints 
may  occur  from  the  formation  of  osteophytes,  thickening 
of  the  capsules,  and  retraction  of  muscles.  The  cartilages 
become  worn  away  at  the  centres,  and  the  ends  of  the 
bones  become  eburnated  by  attrition  and  chronic  osteitis. 
In  such  joints  grating  is  readily  obtained  by  rubbing  the 
eburnated  ends  of  the  bones  against  each  other.  The 
locking  of  the  joints,  which  sometimes  ultimately  occurs, 
is  not  due  to  true  ankylosis,  but  to  the  presence  of  the 
projecting  osteophytes,  and  to  the  thickening  of  the 
capsules  of  the  joints.  True  ankylosis  only  occurs  in  the 
spinal  column  in  cases  of  rheumatoid  arthritis.  Atrophy 
of  the  muscles  from  disuse  is  present  in  bad  cases,  with 
contractures  tending  to  flex  the  thigh  or  to  bend  the  knee 
or  elbow.  There  is  usually  some  increase  of  myotatic 
irritability,  as  shown  by  some  exaggeration,  frequently 
but  slight,  of  the  knee-jerks.  Most  patients  finally  reach 
a  stage  in  which  the  disease  becomes  arrested,  so  that 
they  are  free  from  pain,  and  only  are  troubled  with  the 
associated  crippling  and  consequent  inconvenience. 

Rheumatoid  arthritis  is  nearly  always  associated  with 
a  certain  amount  of  anaemia,  the  patients  presenting  a 
sallow  appearance.  Increased  rapidity  of  the  heart's 
action  is  a  not  uncommon  accompaniment  of  the  disease 
in  its  earlier  stages,  and  cold  and  moist  hands  and  feet 
are  commonly  met  with.  Subcutaneous  fibroid  nodules 
and  periosteal  nodes  are  occasionally  present,  especially 
in  those  cases  which  are  secondary  to  rheumatism  ;  and 
a  rheumatoid  pigmentation  of  the  skin,  somewhat  resem- 
bling freckles  in  appearance,  is  not  unfrequently  seen, 
but  is  especially  present  in  the  acute  stage.  In  a  small 
proportion  of  cases  a  neuritis  is  present,  but  it  probably  is 
always  secondary  to  the  arthritis,  and  may  be  caused, 
as  suggested  by  Bannatyne,  either  by  the  existing  joint 
inflammatory  process,  or  by  the  action  of  toxins  circulating 
in   the  blood.     Spender  describes  the  following  collateral 


Chap,  ix]  RHEUMATISM.  155 

symptoms,  one  or  more  of  which  are  commonly  present, 
as  aids  to  diagnosis  in  doubtful  cases  : — (i)  tachycardia  ; 
(2)  pigmentation  of  the  face,  and  perhaps  numerous  spots 
or  stains  on  the  arms  ;  (3)  cold  and  moist  hands  ;  (4) 
neuralgic  twinges  in  the  upper  and  lower  limbs  ;  (5)  per- 
sistent neuralgic  pain  over  the  ball  of  the  thumb  and  on 
the  ulnar  side  of  the  wrist. 

Rheumatism. — Rheumatism  is  a  disorder  which  gener- 
ally manifests  itself  as  acute  rheumatism  or  rheumatic 
fever  ;  but  in  the  chronic  condition,  although  it  generally 
manifests  itself  as  an  arthritic  disorder — that  is  to  say, 
a  disorder  affecting  the  joints — it  may  not  manifest  itself 
that  way  at  all  :  it  may  simply  show  itself  by  the  pro- 
duction of  chorea,  or  by  the  production  of  erythema,  or 
by  the  production  of  fibrous  nodules,  or  by  the  production 
of  endocarditis  or  pericarditis.  Therefore  rheumatism  is  a 
disorder  which  does  not  necessarily  show  itself  as  a  joint 
affection  ;  it  may  become  manifest  in  some  other  way. 
In  other  words,  there  is  the  articular  chronic  rheumatism 
and  there  is  the  abarticular  chronic  rheumatism — such  as 
the  choreic  and  erythematous  forms. 

As  an  assistance  in  the  diagnosis  of  a  chronic  articular 
affection,  there  is  a  rough  but  fairly  sure  test  which  is 
frequently  of  assistance  in  diagnosis  :  it  is  treatment 
with  salicylate  of  soda.  If  the  case  responds  well  to  this 
treatment,  it  is  a  case  of  rheumatism.  If  it  does  not 
respond  to  this  treatment,  the  existence  of  rheumatoid 
arthritis  or  gout  is  fairly  certain,  as  neither  of  these  affections 
responds  well  to  salicylates.  When  I  hear  the  remark 
about  "  an  obstinate  case  of  rheumatism  which  has  not 
done  well  with  salicylates,"  I  feel  fairly  sure  that  it  is  a 
case  of  gout  or  of  rheumatoid  arthritis — more  probably 
the  latter.  Very  many  of  the  cases  diagnosed  as  chronic 
rheumatism  are  cases  of  rheumatoid  arthritis,  or  gout,  or 
some  form  of  infective  arthritis  or  arthropathy. 

Though  much  less  frequent  than  is  generally  supposed, 


156        GOUT:    .ETIOLOGY    AND    VARIETIES.  [Parx  ii. 

chronic  rheumatic  affections  of  the  joints  do  occur,  but 
they  never  produce  that  permanent  deformity  which  the 
other  affections  may,  especially  the  lipping  of  the  cartilages 
and  the  bony  outgrowths  already  referred  to.  These  chronic 
rheumatic  affections  of  the  joints  are  generally  accom- 
panied by  the  formation  of  fibrous  nodules  over  the  tendons, 
by  the  development  of  extra-articular  fibrous  thickening, 
by  the  presence  of  subcutaneous  fibres,  fibrous  nodules 
(especially  on  the  fingers,  elbows,  and  head),  and  not  un- 
frequently  by  the  indication  of  valvular  disease  of  the 
heart.  There  is  generally  a  well-marked  history  of  rheu- 
matism, and  the  disease  is  identical  with  that  described 
as  "  chronic  fibrous  rheumatism."  It  must  not  be  con- 
sidered that  the  subcutaneous  fibrous  nodules  occur  only 
in  connection  with  rheumatism.  They  are  fairly  frequently 
seen  in  cases  of  rheumatoid  arthritis,  and  less  frequently 
in  gout,  syphilis,  influenza,  and  other  diseases. 

It  should  be  carefully  remembered  that  chronic  rheu- 
matism is  not  associated  with  the  formation  of  bony  or 
cartilaginous  deposits  in  the  joints.  It  shows  little  sym- 
metry, and  is  usually  associated  with  rheumatic  pains 
shifting  about  from  one  place  to  another.  It  never  affects 
the  temporo-maxillary  joints.  As  regards  the  actual 
diagnosis  of  rheumatism,  it  is  usually  fairly  easy.  If  a 
patient  complains  of  pains  in  the  joints,  which  pain  flies 
about  from  joint  to  joint,  and  generally  affects  some  of 
the  muscles  at  the  same  time,  and  if,  in  connection  with 
these  flying  pains,  there  are  indications  of  the  presence 
of  the  rheumatic  erythema — erythema  nodosum — then 
the  diagnosis  of  rheumatism  is  obvious.  As  a  rule,  the 
fitful  way  in  which  the  joints  are  affected,  the  fairly  rapid 
subsidence  of  the  swellings  of  the  joints,  and  the  asso- 
ciation of  muscular  pains,  make  the  diagnosis  a  simple 
matter.  Then  the  response  of  the  disease  to  treatment 
by  salicylates  will  settle  the  diagnosis.  The  absence  of 
bony    thickening   and   of   bony   grating    distinguishes   the 


Chap,  ix]   GOUT  AND  RHEUMATOID  ARTHRITIS.      157 

disease  from  rheumatoid  arthritis,  and  in  addition  the 
finger-joints  are  much  less  frequently  affected. 

Differential  diag'nosis  of  grout  and  rheumatoid 
arthritis. — These  are  the  two  chronic  joint  diseases  which 
are  most  frequently  confounded. 

The  following  distinguishing  characters  show  how  very 
different  the  two  diseases  are.  In  the  first  place,  rheu- 
matoid arthritis  occurs  most  commonly  in  females  ;  gout 
occurs  mostly  in  males.  Rheumatoid  arthritis  occurs 
more  commonly  amongst  the  poor  and  ill-nourished  ;  gout 
mostly  among  the  well-to-do  and  well-nourished.  Rheu- 
matoid arthritis  is  a  disease  which  is  improved  by  good 
dieting  ;  in  the  case  of  a  gouty  person  a  spare  and  plain 
diet  is  indicated.  The  onset  of  rheumatoid  arthritis  is 
insidious  ;  that  of  gout  sudden  and  obvious.  As  regards 
the  commencement  of  the  attack,  gout  most  commonly 
begins  in  one  of  the  feet,  especially  in  the  great  toe  joint  ; 
rheumatoid  arthritis,  although  ultimately  it  frequently 
affects  many  joints  of  both  hands,  nearly  always  begins  in 
one  joint,  most  commonly  selecting  one  of  the  joints  of  the 
thumb,  either  the  carpo-metacarpal  or  metacarpo-phalangeal 
joint,  after  which  it  rapidly  spreads  to  the  other  joints. 
Then  as  regards  the  appearance  :  in  the  case  of  rheumatoid 
arthritis  there  is  no  obvious  swelling  at  first,  and  no  marked 
redness.  In  the  case  of  gout,  at  its  commencement  there 
is  very  obvious  swelling,  marked  redness,  and  a  shiny 
condition  of  the  skin  around  the  affected  joint. 

In  rheumatoid  arthritis  there  is  very  little  pain  at  first. 
There  is  some  aching  in  the  joint,  but  it  starts  in  a  very 
insidious  manner.  It  is  this  insidious  character  of  the 
disease  which  is  one  of  its  bad  features,  for  the  patients 
do  not  seek  advice  until  the  affection  is  fairly  advanced. 
Gout,  however,  begins  in  the  most  marked  manner  with 
severe  pain,  the  patient  as  a  rule  waking  up  in  the  early 
morning  with  excruciating  pain  in  the  great  toe.  There- 
fore, if  there  is  doubt  as  to  whether  a  particular  case  is 


158        GOUT:    .ETIOLOGY    AND    VARIETIES,  [part  ii. 

one  of  rheumatoid  arthritis  or  of  gout,  the  patient  should 
be  questioned  as  to  the  commencement  of  the  attack,  in 
order  to  ascertain  whether  it  began  with  an  obvious  out- 
burst of  pain,  and  with  sweUing  and  redness  of  the  joint, 
or  whether  it  began  very  insidiously.  Then  as  to  the  joint 
affections  :  apart  from  what  has  been  stated  as  to  gout 
generally  beginning  in  the  foot,  and  rheumatoid  arthritis 
generally  in  the  hand,  there  is  one  joint  commonly  affected 
in  rheumatoid  arthritis  which  is  not  affected  in  cases  of 
gout — that  is  the  temporo-maxillary  articulation.  I  have 
never  seen  a  case  of  gout  in  which  the  temporo-maxillary 
joint  has  been  affected,  whereas  in  rheumatoid  arthritis 
it  is  fairly  common  for  that  joint  to  be  affected. 

In  rheumatoid  arthritis  there  is  a  special  liability  to 
the  affection  of  the  joints  of  the  cervical  vertebrae,  as 
evidenced  by  pain  and  stiffness  at  the  back  of  the  neck. 
This  is  a  most  useful  distinguishing  sign.  Another  dis- 
tinction is  this — and  it  is  perhaps  one  of  the  most  important 
distinctions — that  in  connection  with  rheumatoid  arthritis 
there  is  a  remarkable  symmetry  in  the  affection  of  the 
smaller  joints  of  the  hands.  In  gout  that  symmetry  is 
wanting.  It  was  this  symmetrical  affection  of  the  joints 
which  led  to  the  idea — which  I  believe  to  be  absolutely 
erroneous — that  rheumatoid  arthritis  is  a  nervous  disease. 
Lastly,  in  a  case  of  rheumatoid  arthritis  sodium  biurate  is 
found  neither'  in  the  joints  nor  in  the  blood,  whereas  in 
the  gouty  person  sodium  biurate  exists  both  in  the  joints 
and  in  the  blood. 

It  is  not  common  to  get  rheumatoid  arthritis  and  gout 
associated  in  the  same  individual.  Undoubtedly  rheuma- 
toid arthritis  may  supervene  in  joints  which  have  been  the 
seat  of  any  acute  infective  arthritis.  Any  affection  which 
impairs  the  nutrition  or  weakens  the  resistance  of  joints 
offers  a  suitable  condition  for  the  development  of  rheu- 
matoid arthritis.  Hence  rheumatoid  arthritis  may  follow 
such   diseases   of   the   joints   as   acute    rheumatism,    gout. 


Chap.  IX.]  STILL'S    DISEASE.  159 

gonorrhoeal  arthritis,  etc.  This  is  the  only  sense  in  which 
such  diseases  are  related  to  rheumatoid  arthritis,  in  that 
they  have  by  impairment  of  the  joint  structures  so 
lowered  the  vitality  as  to  render  the  joints  more  liable  to 
the  invasion  of  the  micro-organism  or  toxin  of  rheuma- 
toid arthritis.  On  the  other  hand,  a  person  suffering  from 
rheumatoid  arthritis,  who  indulges  in  rich  living  for  a 
lengthened  period  of  time,  and  especially  if  he  takes  much 
wine,  may  develop  gout,  and  so  gouty  deposits  in  the  joints 
of  a  patient  suffering  from  rheumatoid  arthritis  may 
occasionally  be  met  with.  This,  however,  is  only  a  com- 
plication ;  there  is  no  actual  relationship  between  the  two 
conditions,  and  one  disease  does  not,  in  the  strict  sense 
of  the  term,  predispose  to  the  other. 

A  form  of  chronic  joint  disease  in  children  de- 
scribed by  Still. — This  is  a  disease  closely  resembling  the 
rheumatoid  arthritis  of  adults,  and  which  until  recently 
was  always  considered  to  be  identical  with  rheumatoid 
arthritis,  but  which,  as  pointed  out  by  Still,  presents  such 
marked  differences  as  to  suggest  that  it  has  a  distinct 
pathology. 

The  disease  consists  of  a  chronic  progressive  enlarge- 
ment of  joints  associated  with  enlargement  of  glands 
and  enlargement  of  the  spleen.  The  onset,  which  is  usually 
insidious,  almost  always  occurs  before  the  second  dentition, 
and  girls  are  more  commonly  affected  than  boys.  The 
enlargement  of  the  joints  is  smooth  and  fusiform,  and  feels 
like  a  general  thickening  of  the  tissues  around  the  joint, 
with  none  of  the  bony  irregularities  of  the  rheumatoid 
arthritis  of  adults.  There  is  no  redness,  and  as  a  rule  no 
tenderness  of  the  joints  ;  and,  although  creaking  is  fre- 
quently present,  there  is  never  any  of  the  bony  grating 
so  commonly  present  in  true  rheumatoid  arthritis,  since 
in  this  disease  there  is  a  complete  absence  of  the  cartilaginous 
changes  so  characteristic  of  the  latter  disease.  Limitation 
of  movement,  chiefly  of  extension,  is  almost  always  present. 


i6o        GOUT:    ETIOLOGY    AND    VARIETIES,   [part  ii. 

There  is  an  absence  of  the  extensive  deformities  of  the 
hands  so  frequently  present  in  the  rheumatoid  arthritis 
of  adults.  The  affection  is  symmetrical.  The  joints 
earliest  affected  are  usually  the  knees,  wrists,  and  those  of 
the  cervical  spine  ;  the  ankles,  elbows,  and  fingers  are 
subsequently  affected.  There  is  no  tendency  to  suppuration 
nor  to  bony  ankylosis.  One  of  the  most  distinctive  features 
is  the  affection  of  the  lymphatic  glands.  The  enlargement 
is  general,  but  affects  primarily  and  chiefly  those  related 
to  the  joints  affected.  The  enlargement  of  the  spleen  is 
roughly  proportionate  to  that  of  the  glands,  but  does  not 
extend  to  more  than  half-an-inch  to  one  inch  below  the 
costal  margin.  The  heart  shows  no  evidence  of  valvular 
disease.  Sweating  is  often  profuse,  and  a  certain  amount 
of  pyrexia,  generally  recurrent  in  character,  may  be  present. 
The  disease  is  usually  accompanied  by  a  general  arrest  of 
bodily  development.  The  disease  is  not  in  itself  fatal,  but, 
after  running  a  slow  course,  the  joint  disease  becomes 
permanently  stationary. 

The  four  important  points  in  the  differential  diagnosis 
of  this  disease  from  rheumatoid  arthritis  are  (i)  the  enlarge- 
ment of  the  glands  ;  (2)  the  enlargement  of  the  spleen  ; 
(3)  the  peculiar  appearance  and  feel  of  the  joints,  with 
the  absence  of  bony  grating  on  manipulation,  and  the 
absence  of  osteophytic  outgrowths  ;  and  (4)  the  fact  that 
the  disease  begins  nearly  always  in  the  knees  or  wrists, 
and  affects  the  fingers  much  later,  whereas  rheumatoid 
arthritis  in  adults  affects  the  small  joints  of  the  hands 
early,  and  frequently  commences  in  them. 

Senile  arthropathies. — Senile  arthritis  in  the  great 
majority  of  cases  affects  only  one  joint,  usually  the  hip 
or  shoulder.  Occasionally  it  occurs  in  the  spinal  column. 
This  is  the  form  of  arthritis  frequently  known  as  the 
monarticular  form  of  rheumatoid  arthritis,  but  it  should 
be  regarded  as  a  local  degeneration,  progressive  in  its 
nature.     It  is,  I  believe,  an  entirely  different  disease  from 


Chap.  IX.]  GONORRHCEAL    ARTHRITIS.  i6i 

rheumatoid  arthritis,  and  is  probably  not  microbic  in  origin. 
In  the  hip  the  disease  is  known  as  "  morbus  coxae  seniHs," 
and  in  the  spine  it  is  known  as  "  spondyhtis  deformans." 
It  occurs  in  elderly  people,  and  is  in  the  majority  of  cases 
started  by  some  local  injury,  and  is  common  in  old  persons 
who  have  had  to  carry  heavy  weights,  or  who  make  ex- 
cessive use  of  their  lower  limbs  in  the  course  of  their  occu- 
pation. The  arthritis  is  persistent,  and,  if  not  suitably 
treated,  progressive.  Grating  is  nearly  always  present, 
with  muscular  wasting,  shortening  of  the  limb,  and  limita- 
tion of  movement  accompanied  by  pain.  On  deep  pres- 
sure over  the  affected  joint  pain  is  always  ehcited.  The 
synovial  membrane  of  the  joint  shows  chronic  inflammatory 
changes,  along  with  destruction  of  cartilages  and  softening 
of  the  articular  ends  of  the  bones.  The  last-mentioned 
condition  is  in  marked  contrast  to  the  eburnation  of  the 
ends  of  the  bones  in  cases  of  rheumatoid  arthritis. 

Gonorrhoea!  arthritis.— This  form  of  arthritis  is  also 
known  as  "  gonorrhoeal  rheumatism,"  a  term  which  should 
be  abandoned  as  being  misleading  in  its  character.  It 
is  always  secondary  to  a  gonorrhceal  attack  elsewhere. 
This  attack  is  generally  in  the  urethra,  but  is  not  necessarily 
so,  as  some  cases  have  followed  infection  of  the  conjunctiva. 
The  arthritis  is  due  to  the  presence  of  the  gonococcus  in 
the  joints.  It  usually  appears  at  the  decline  of  the  urethritis, 
or  even  when  this  appears  to  be  cured.  It  is  not,  there- 
fore, directly  proportional  to  the  acuteness  of  the  urethritis. 
It  rarely  develops  before  the  third  week,  and  its  advent 
may  be  postponed  for  several  months  after  the  onset  of 
the  gonorrhoea.  Time  is  required  for  the  gonococci  to 
reach  the  glandular  tissues  of  the  prostate,  whence  they 
are  enabled  to  enter  the  circulation.  This  form  of  arthritis 
is  most  liable  to  affect  the  larger  joints,  especially  the 
knees  ;  the  joints  that  may  also  be  affected  are  the  ankles, 
elbows,  small  joints  of  the  feet,  shoulders,  wrists,  small 
joints  of  the  hands,  and  the  sterno-clavicular  joints. 
I. 


i62       GOUT:    ETIOLOGY    AND    VARIETIES,  [part  ii. 

The  disease  is  apt  to  be  mistaken  for  subacute  rheu- 
matism, but  it  may  be  differentiated  by  the  comparative 
absence  of  temperature,  and  by  the  non-reaction  of  the 
affection  to  sahcylates.  As  a  rule  the  diagnosis  is  rendered 
easy  by  the  presence  of  a  gonorrhoeal  discharge,  but  this 
is  apt  to  be  overlooked  in  women,  on  account  of  the  fre- 
quency of  a  leucorrhoeal  discharge. 

The  actual  condition  of  gonorrhoeal  arthritis  may  be 
one  of  synovial  effusion,  or  it  may  be  limited  to  thickening 
of  the  joint  capsule  and  of  the  periarticular  tissues.  If 
neglected,  suppuration  may  occur  in  the  joint. 

A  form  of  infective  arthritis  which  is  somewhat  akin  to 
gonorrhoeal  arthritis  is  that  accompanying  ophthalmia 
neonatorum.  Rapid  recovery  always  follows  on  fixation 
of  the  affected  limb  and  local  treatment  of  the  ophthalmia. 
Two  other  forms  of  septic  or  infective  arthritis  somewhat 
resembling  gonorrhoeal  arthritis  are  those  which  occasion- 
ally occur  in  connection  with  profuse  leucorrhoeal  dis- 
charges, and  in  connection  with  bronchiectasis. 

Arthropathies  due  to  infective  fevers. — In  this 
chapter  I  am  dealing  only  with  the  chronic  forms  of  arthritis, 
but  it  is  necessary  to  refer  briefly  to  the  forms  of  arthritis 
which  may  occur  in  connection  with  any  of  the  infective 
fevers.  As  generally  seen,  these  are  forms  of  acute  arthritis, 
but  occasionally  they  persist  for  a  long  time,  and  so  become 
cases  of  chronic  arthritis.  These  forms  of  arthritis  have 
been  known  to  occur  in  connection  with  scarlet  fever, 
pneumonia,  malaria,  septicaemia,  pyaemia,  enteric  fever, 
Maltese  fever,  measles,  influenza,  dysentery,  glanders, 
erysipelas,  etc.  It  is,  however,  only  within  the  last  few 
years  that  the  joint  troubles  that  occasionally  occur  in 
the  course  of  the  specific  diseases  have  come  to  be  regarded 
as  due  to  the  micro-organisms  or  poisons  of  the  respective 
diseases.  Formerly  they  were  looked  on  as  manifestations 
of  true  rheumatism  occurring  during  the  course  of  the 
disease.     All  these  forms  of  arthritis  are  especially  liable 


Chap,  ix.i  INFECTIVE    ARTHRITIS.  163 

to  occur  in  a  joint  or  joints  which  have  been  previously 
damaged,  either  by  disease  or  by  mechanical  injury. 

Scarlatinal  arthritis. — This  is,  perhaps,  the  best  known 
type  of  arthritis  met  with  in  the  various  infective  diseases. 
The  elbows  and  knees  are  the  joints  most  frequently 
affected  ;  the  smaller  joints  of  the  upper  extremities  follow 
next. 

Pneumococcic  arthritis. — The  occurrence  of  arthritis 
during  an  attack  of  pneumonia  has  long  been  known,  but 
until  comparatively  recently  it  was  generally  ascribed  to 
a  concurrent  attack  of  rheumatism,  and  was  not  directly 
connected  with  the  attack  of  pneumonia.  A  strong  tendency 
to  ankylosis  is  one  of  the  special  characteristics  of  an  in- 
fective arthritis.  Previous  damage  to  a  joint,  as  by  injury, 
rheumatism,  or  gout,  favours  the  localisation  of  pneumo- 
coccic arthritis.  The  influence  of  injuries  in  predisposing 
joints  to  attacks  of  infective  or  septic  arthritis  should  be 
carefully  borne  in  mind,  as  otherwise  cases  which  are 
really  those  of  infective  arthritis  may  be  considered  simply 
traumatic  in  origin,  and  so  the  possibly  necessary  operative 
treatment  of  the  joint  may  never  be  considered. 

Malarial  arthritis. — The  parasite,  although  different  in 
its  life  history  from  a  bacterium,  yet  from  the  point  of 
view  of  causation  of  arthritis  may  be  considered  as  such. 
Malarial  arthritis  due  to  the  parasite  is  a  comparatively 
rare  affection,  but  rheumatoid  arthritis  coincident  with  a 
malarial  attack  is  not  by  any  means  uncommon. 

Quiet  elTusion  into  knee-joints.— This  affection  was 
first  described  by  Sir  Wilham  H.  Bennett,  and  was 
stated  by  him  to  occur  only  in  girls  and  women,  and  to 
be  always  associated  with  menstrual  irregularity  or  uterine 
trouble.  It  occurs  mainly  at  the  time  of  puberty,  and  at 
the  climacteric.  A  similar  condition  has,  however,  been 
observed  in  males.  The  affection  consists  of  a  passive 
effusion  into  the  joint,  and  rarely  occurs  in  any  other  joint 
than  the  knee.     It  is  unattended  by  pain,  and  a  large  number 


i64       GOUT:    ETIOLOGY    AND    VARIETIES,  [part  ii. 

of  the  patients  are  unaware  of  its  existence,  unless  attention 
is  called  to  it  accidentally.  It  is  best  recognised  when  the 
patient  is  standing  in  the  upright  position,  when  the  fluid 
sinks  to  the  lower  part  of  the  joint  cavity,  and  sometimes 
forms  a  pouch-like  overhanging  of  the  synovial  membrane 
at  its  lower  anterior  aspect.  Attention  is  generally  called 
to  the  condition  by  a  slight  injury,  such  as  a  twist  or  fall. 
The  joints  of  the  two  sides  are  usually  involved  at  the  same 
time,  but  the  effusion  is,  as  a  rule,  much  more  marked  on 
one  side  than  on  the  other,  that  on  the  right  side  being 
generally  the  greater. 

Nerve  deg^enerative  arthropathies. — These  are  joint 
affections  that  occur  in  tabes,  ataxy,  paraplegia,  progressive 
muscular  atrophy,  etc.  The  joint  troubles  are  due  to 
abnormal  trophic  influences  started  by  affections  of  the 
central  nerve  organs,  as  the  result  of  which  inflammatory 
troubles,  generally  of  a  very  chronic  nature,  are  set  up, 
characterised  by  alterations  in  the  ends  of  the  bones, 
ulceration  of  cartilages,  and  formation  of  fibrous  adhesions. 
Of  all  the  chronic  joint  affections  these  are  perhaps  the 
easiest  of  diagnosis,  on  account  of  their  association  with 
an  easily  recognisable  disease  of  the  nervous  system  of 
a  degenerative  nature. 

Tuberculous  disease. — The  history  of  the  case,  both 
family  and  personal,  is  of  great  assistance  in  making  a 
diagnosis  in  this  form  of  joint  disease.  The  swelling  is 
frequently  spindle-shaped.  When  the  disease  is  advanced 
the  joint  is  in  a  condition  of  organised  fibrous  tuberculosis, 
and  consequently  nothing  of  diagnostic  value  is  to  be  made 
out  by  radiographs. 

Syphilitic  joint  disease. — This  is  commonly  chronic. 
There  is  effusion  with  thickening  of  the  capsules  of  the 
medium-sized  and  larger  joints,  with  occasional  bony 
thickening  and  lipping  of  the  smaller  joints,  which  may 
at  times  closely  simulate  rheumatoid  arthritis.  The  pres- 
ence of  a  gumma,  and  of  old  iritis  and  other  indications 


Chap.  IX.]  DISEASES    OF    JOINTS.  165 

of  syphilis,  will  frequently  assist  in  making  a  correct  diag- 
nosis. A  form  of  joint  disease  occurring  in  the  later  stages 
of  syphilis  has  been  described  by  Whitfield,  which  presents 
many  resemblances  to  a  joint  recovering  from  acute  gout. 
The  joint  is  considerably  swollen,  the  surface  shiny,  the 
skin  being  of  a  dark  red  colour,  with  distended  veins  cross- 
ing over  the  joint.  As  a  rule,  it  is  exquisitely  tender  to 
the  touch.  The  diagnosis  is,  as  a  rule,  rendered  easy  by 
the  discovery  of  a  periosteal  gumma  over  one  of  the  bones. 
The  joint  disease  itself  is  undoubtedly  gummatous  in 
nature,  the  gummatous  infiltration  starting  in  the  liga- 
ments and  periarticular  tissues. 

Pulmonary  osteo-arthropathy. — This  is  a  rare  dis- 
ease. It  is  secondary  to  some  chronic  pulmonary  disease, 
such  as  phthisis,  empyema,  and  chronic  bronchitis.  The. 
disease  may  possibly  be  tuberculous,  or  be  due  to  some 
toxic  agent.  It  is  characterised  by  considerable  enlarge- 
ment of  the  hands,  wrists,  feet,  and  ankles.  It  is  apt  to 
be  mistaken  for  acromegaly,  but  may  be  distinguished  by 
the  clubbing  of  the  finger  ends  and  the  enlargement  of 
the  wrists,  which  conditions  are  absent  in  acromegaly. 

Joint  changes  in  Raynaud's  disease. — The  joints 
are  much  thickened  ;  they  present  little  indication  of  fluid 
distension  of  the  cavities  ;  there  is  a  good  deal  of  thicken- 
ing of  the  bone,  and  considerable  pain  and  tenderness. 
The  condition  is  apt  to  be  mistaken  for  rheumatoid  arthritis, 
but  the  diagnosis  is  rendered  easy  by  .the  association  with 
the  circulatory  changes  accompanying  Raynaud's  disease. 

Distinction  of  so-called  chronic  rheumatism  (flbro- 
sitis)  from  gout. — Many  cases  of  so-called  chronic  rheu- 
matism are  frequently  confounded  with  gout.  These  are 
cases  in  which  the  essential  pathological  change  is  an  in- 
flammatory hyperplasia  of  the  white  fibrous  tissue  in 
various  parts  of  the  body,  to  which  the  term  "  fibrositis  " 
has  been  very  aptly  applied.  The  articular  structures 
proper — synovial  membrane,  cartilage,  and  bone — are  not 


i66       GOUT:    .ETIOLOGY    AND    VARIETIES.  [Part  ii. 

primarily  affected,  but  the  parts  implicated  are  the  fibrous 
tissues  of  the  joints,  muscles,  and  bones,  especially  the 
aponeuroses  and  insertions  of  the  muscles,  fasciae,  the 
fibrous  ligaments  of  the  joints,  and  the  periosteum.  Such 
affections  cause  pain  and  stiffness  in  these  structures,  are 
especially  apt  to  recur,  and  are  commonly  referred  to  as 
rheumatic  or  even  gouty  in  their  origin.  This  inflammatory 
hyperplasia  of  the  fibrous  tissues  occurs  in  patches,  and  is 
started  by  exposure  to  wet  or  cold,  by  injury,  or  by  some 
irritant,  microbic  or  toxic,  conveyed  in  the  blood.  The 
inflamed  and  swollen  fibrous  tissue  is  tender,  painful  on 
pressure  or  on  movement,  and  can  frequently  be  felt  on 
palpation,  or  is  evident  by  the  consequent  elevation  of  the 
skin.  This  fibrositis  may  completely  disappear,  but  recur- 
rences are  common,  and  if  not  suitably  treated  the  thickened 
fibrous  tissue  remains  as  indurations  at  various  parts. 

The  indurations  may  be  widespread  but  generally  are 
well  defined,  and  vary  in  size  from  an  eighth  of  an  inch  to 
one  inch  in  diameter.  They  may  be  situated  in  the  sub- 
cutaneous tissue,  the  muscles,  tendons,  aponeuroses,  and 
periosteum.  The  pain  is  especially  aggravated  by  any 
sudden  movement  of  the  muscles  which  compresses  or 
stretches  the  affected  fibrous  tissues  and  the  sensory  nerve 
filaments.  The  muscle-spindles,  which  lie  between  the 
bundles  of  muscular  fibres  and  in  the  fibrous  tissue  of  the 
muscle,  and  each  one  of  which  receives  one  or  more  narrow 
muscular  fibres,  and  two  or  more  nerve-fibres,  are  the  only 
sensory  structures  in  muscle,  and  it  is  through  them  that 
the  pain  of  so-called  muscular  rheumatism  is  felt.  Owing 
to  direct  pressure  of  a  fibrous  nodule  on  a  nerve,  or  to  the 
involvement  of  the  nerve  in  the  nodule,  the  pain  may  be 
felt  over  an  extensive  area,  or  even  be  referred  to  a  part 
of  the  body  which  is  not  the  seat  of  the  fibrositis. 

Etiology. —  Local  fibrositis  may  result  from  several 
causes,  of  which  the  following  are  the  commonest  : — 

(i)  Cold,  damp,  and  wet. — In  a  very  large  number  of 


Chap,  m  FlBRQSlTlS.  167 

cases  the  only  assignable  cause  of  the  fibrositis  is  a  history 
of  exposure  to  cold  and  wet.  Sometimes  the  attack  comes 
on  acutely  a  few  hours  after  the  exposure,  as  in  many  cases 
of  lumbago,  stiff  neck,  intercostal  "  rheumatism,"  and 
other  forms  of  so-called  muscular  "  rheumatism."  At 
other  times  stiffness  gradually  develops  after  the  exposure, 
and  passes  on  to  the  condition  of  chronic  fibrositis  generally 
known  as  chronic  rheumatism. 

The  exposure  may  be  due  to  draughts,  remaining  in 
wet  clothes,  lying  or  sitting  on  damp  ground  or  some  cold 
substance,  or  the  simple  advent  of  damp  or  cold  weather. 
Many  persons  are  readily  affected  by  the  approach  of  rain, 
and  by  a  lowering  of  the  barometric  pressure.  Longstreth 
states  that  the  painful  symptoms  do  not  correspond  to 
rain,  but  to  the  fall  of  barometric  pressure,  and  Stockman 
suggests  that  possibly  the  atmospheric  changes  may  increase 
or  lessen  the  lymph-pressure  in  the  body,  and  so  increase 
or  lessen  the  tension  in  the  affected  fibrous  tissues.  A  very 
common  cause  of  lumbago  from  exposure  to  a  local  draught 
is  sitting  on  a  draughty  privy  or  water-closet  ;  this,  no 
doubt,  accounts  for  the  prevalence  of  that  affection  in  rural 
districts,  combined  with  the  constant  strain  of  the  lumbar 
muscles,  amongst  so  many  agricultural  labourers. 

(2)  Extremes  of  heat  and  cold. — Sudden  and  considerable 
variations  in  temperature  constitute  by  no  means  an  un- 
common cause  of  a  generalised  fibrositis  which  takes  the 
form  of  so-called  "  muscular  rheumatism,"  following  on 
the  resulting  chill.  One  of  the  severest  cases  of  fibrositis 
(muscular  rheumatism)  that  I  have  ever  seen  was  the  case 
of  a  stoker  who  after  working  during  very  hot  weather  in 
the  engine-room  of  a  steamer  on  the  Red  Sea  went  straight 
to  the  refrigerating  chamber  of  the  steamer  in  order  to 
cool  himself.  The  result  was  a  very  severe  attack  of  in- 
flammation of  the  fibrous  tissues  over  practically  the  whole 
of  the  body,  which  absolutely  prostrated  him,  and  from 
which  he  made  a  very  tedious  recovery. 


i68       GOUT  :    ^ETIOLOGY    AND    VARIETIES,    [pari  il 

(3)  Local  injuries. — These  are  responsible  for  a  large 
number  of  cases  of  local  fibrositis,  so-called  "  local  rheu- 
matism." The  injury  is  generally  caused  by  muscular  over- 
exertion, such  as  the  strain  of  lifting  a  heavy  weight,  the 
strain  exerted  in  certain  muscles  in  order  to  save  a  sudden 
fall,  and  the  excessive  muscular  strain  that  an  athlete 
may  put  forth.  Golf  produces  a  number  of  such  injuries, 
the  fibrous  tissue  of  the  muscles  of  the  arms  and  back  and 
their  attachments  being  specially  affected  in  this  game. 

If  the  individual  has  previously  suffered  from  fibrositis 
which  has  not  been  completely  cured,  or  which  has  left 
some  fibrous  nodules,  a  comparatively  slight  wrench  may 
be  sufficient  to  start  the  aching  in  the  affected  part. 

(4)  Absorption  of  irritating  toxins  from  the  gastro-intestinal 
tract. — It  has  long  been  recognised  that  disorders  of  the 
stomach  or  bowels  may  give  rise  to  "  rheumatic  "  pains. 
The  aching  in  the  joints  and  the  lumbar  region  that  occa- 
sionally occurs  the  day  after  a  lengthy  dinner,  especially  if 
several  wines  have  been  indulged  in,  is  due  to  irritation 
of  the  fibrous  tissues  by  the  toxins  absorbed  from  the 
intestinal  tract,  and  which  have  been  produced  there  by 
abnormal  fermentation. 

This  pain,  whether  in  the  joints  or  the  lumbar  region, 
which  follows  excessive  indulgence  at  the  table  is  generally 
attributed  to  gout,  and,  as  a  rule,  the  champagne,  claret, 
or  port  is  blamed  for  it.  I  am  convinced,  however,  that 
this  articular  or  muscular  pain  has,  in  the  great  majority 
of  cases,  no  relation  whatever  to  gout,  and  that  it  is  simply 
an  indication  of  an  inability  of  the  gastro-intestinal  tract 
to  deal  properly  with  the  various  articles  introduced  into 
it. 

(5)  Tonsillitis  and  -pharyngitis. — The  aching  pains  that 
occur  in  various  parts  of  the  body  in  connection  with  these 
affections  are  well  known,  and  are  doubtless  due  to  toxic 
absorption  and  consequent  irritation  of  the  fibrous 
tissues. 


Chap. IX.]  MUSCULAR    RHEUMATISM.  169 

(6)  Influenza. — The  majority  of  us  are  probably  person- 
ally acquainted  with  the  aches  and  even  severe  pains  in 
the  muscles,  joints,  and  bones  which  accompany  this  disease. 
These  are  in  all  probability  due  to  the  librositis  set  up  by 
the  specific  microbe  or  its  toxin.  It  is  not  uncommon  to 
find  fibrous  nodules  and  thickenings  left  as  sequeke  of  this 
disease. 

(7)  Fehricula. — A  "  feverish  cold  "  is  generally  accom- 
panied by  aching  pains  in  the  muscles,  joints,  and  bones. 
The  attack,  which  is  sometimes  described  as  a  "  rheumatic 
cold  "  or  an  "  influenzal  cold,"  is  probably  microbic  in  its 
origin,  and  the  pains  are,  no  doubt,  due  to  irritation  of  the 
fibrous  tissues  by  the  microbe  or  its  toxin. 

Various  forms  of  fibrositis. — Muscular  rheumatism. 
— This  affection  is  always  a  fibrositis.  Any  of  the 
muscles  may  be  affected.  Affection  of  the  muscles  of 
the  lumbar  region  constitutes  one  of  the  forms  of  lum- 
bago ;  affection  of  the  muscles  of  the  neck  constitutes 
stiff  neck  ;  affection  of  the  deltoid  muscle  consti- 
tutes "  deltoid  rheumatism  ; "  affection  of  the  inter- 
costal muscles  constitutes  "  intercostal  rheumatism."  Tlae 
pain  at  first  is  generally  dull,  but  in  anything  like  severe 
cases  soon  becomes  sharp  and  shooting,  and  is  aggravated 
by  damp  weather.  It  is  usually  worse  when  the  patient 
becomes  warm  in  bed,  and  is  generally  felt  severely  on 
waking  in  the  morning  and  on  rising  from  bed.  Brachial 
fibrositis  is  especially  apt  to  be  of  long  duration,  and  inter- 
feres with  sleep  on  account  of  the  difficulty  of  getting  the 
arm  into  an  easy  position.  To  some  extent  it  wears  off 
with  exercise  or  on  rubbing  the  affected  parts.  It  is  always 
accompanied  by  a  feeling  of  stiffness. 

Lumbago. — This  is  a  very  typical  form  of  fibrositis. 
As  just  mentioned,  it  may  be  an  affection  of  the  fibrous 
elements  of  the  lumbar  muscles,  but  more  commonly  it 
starts  as  a  localised  affection  of  the  insertions  of  the  muscles 
in  the  vicinity  of  one  or  both  of  the  sacro-iliac  joints.     It 


170       GOUT  :    ETIOLOGY   AND    VARIETIES.  [Parx  n. 

spreads  by  continuity  of  the  fibrous  tissue,  as  is  manifested 
by  its  affecting  the  tendinous  attachments  of  the  neigh- 
bouring muscles,  by  its  affecting  the  sacro-ihac  joint  itself, 
and  by  its  often  spreading  through  the  joint  and  reaching 
the  sheath  of  the  sciatic  nerve.  This  explains  the  very 
frequent  association  of  some  degree  of  sciatica  with  an 
attack  of  lumbago.  It  is  astonishing  to  find  in  a  very 
large  number  of  cases  of  lumbago  that  a  careful  examination 
of  the  back  reveals  no  pain  or  tenderness  on  pressure  over 
the  various  muscles,  but  that  as  soon  as  one  or  both 
sacro-iliac  joints  are  pressed  upon,  acute  pain  is  complained 
of  and  the  patient  refers  his  appreciation  of  the  pain  to 
that  region.  I  am  convinced  that  in  the  majority  of  cases 
of  lumbago  the  affection  is  not  in  the  quadratus  lumborum, 
nor  even  in  the  deeper  muscles  of  the  back,  but  is  in  the 
fibrous  tissues  directly  over  the  sacro-iliac  joint,  and  in 
the  joint  itself.  The  production  of  the  pain  of  lumbago 
is  usually  sudden,  the  patient  frequently  ascribing  it  to  a 
sudden  strain  or  rick,  especially  on  rising  in  the  morning, 
but  although  the  production  of  the  pain  is  generally  sudden, 
yet  the  condition  on  which  it  depends  has  been  gradually 
developed. 

Rheumatic  neuralgia. — This  is  a  fibrositis  of  the  nerve- 
sheaths,  and  is  a  common  cause  of  sciatica,  especially  accom- 
panying lumbago  of  the  sacro-iliac  joints.  The  affected 
nerve  is  painful  on  pressure  or  when  stretched.  The 
symptoms  are  numbness,  tingling,  "  pins  and  needles," 
and  pain,  all  of  which  are  due  to  slight  compression  of 
the  nerve. 

Dupuytren's  contraction. — This  is  a  localised  fibrositis 
caused  by  habitual  postural  use  of  the  hand.  It  is  frequently 
ascribed  to  gout,  but,  according  to  my  experience,  the  con- 
dition has  no  connection  with  that  disease.  Certainly  I 
have  never  seen  any  gouty  deposits  in  the  thickened 
tissues,  nor  is  the  affection  commoner  amongst  gouty 
subjects. 


Chap.  IX.]  PROGNOSIS.  I7I 

Prognosis  in  g-out.— If  no  complications  arise,  if  the 
attacks  are  not  too  frequent,  and  if  no  serious  amount  of 
albuminuria  occurs,  the  disease  is  not  likely  materially  to 
shorten  life,  especially  if  the  patient  is  amenable  to  proper 
treatment  and  discipline. 


PART  III 

INVESTIGATIONS  OF  CERTAIN  POINTS 
CONNECTED  WITH  THE  TREATMENT 
OF    GOUT. 

CHAPTER    X. 
SOLUBILITY    OF   SODIUM    BIURA.TE. 

Influence  exerted  by  the  mineral  constituents  of  meat,  milk,  and 
vegetables  respectively  on  the  solubility  of  sodium  biurate — 
Relative  effects  exerted  by  the  mineral  constituents  of  various 
vegetables  on  the  solubility  of  sodium  biurate — Influence 
exerted  by  the  mineral  constituents  of  various  vegetables 
in  retarding  the  conversion  of  sodium  quadriurate  into  sodium 
biurate — The  vegetables   most  beneficial  to   gouty  subjects. 

It  is  well  known  that  the  excessive  consumption  of  rich 
nitrogenous  food,  combined  with  excesses  in  wine  and 
malt  liquors,  both  induces  and  excites  gout.  The  com- 
parative immunity  of  females  and  young  people  from 
gout  is  mainly  explained  by  the  absence  of  such  determining 
causes  of  the  gouty  attack,  combined  with,  in  the  case  of 
young  people,  the  absence  of  predisposing  cause,  and  also 
the  fact  that  the  secreting  functions  are  in  full  activity. 
The  subjects  of  gout  are  generally  persons  who  live  well 
and  consume  a  large  amount  of  animal  food.  Budd, 
speaking  from  a  long  and  extensive  professional  con- 
nection with  a  large  rural  district,  states  that  he  never 
knew  an  instance  of  gout  occurring  among  agricultural 
labourers. 

Though    uric  acid  is  not   the  primary  cause  of  gout, 

172 


CAr.x.]  VEGETABLE    ASHES.  173 

yet  its  deposition  as  sodium  biurate  and  its  subsequent 
absorption  are  materially  influenced  by  various  conditions. 
As  it  is  quite  possible  that  the  different  saline  constituents 
of  animal  and  vegetable  foods  might  very  materially  affect 
the  solubility  of  sodium  biurate  and  therefore  influence 
its  precipitation,  I  thought  it  advisable  to  ascertain  if 
the  saline  substances  contained  in  different  articles  of 
diet  appreciably  affected  the  solvency  of  sodium  biurate 
at  the  temperature  of  the  human  body,  as  obviously  the 
subject  might  have  both  a  pathological  and  therapeutical 
bearing.  The  following  experiments  were  therefore  carried 
out. 

Influence  of  the  mineral  constituents  of  meat,  milk, 
and  vegretables  respectively  on  the  solubility  of  sodium 
biurate  at  100*^  F. — A  series  of  experiments  was  under- 
taken, operating  upon  the  ash  respectively  of  lean  beef, 
milk,  and  mixed  vegetables  (potatoes,  spinach,  and  French 
beans).  The  experiments  were  carried  out  in  the  following 
manner  : — The  contents  of  a  number  of  bottles,  each 
containing  100  c.c.  of  distilled  water,  were  mixed  with 
known  quantities  of  the  different  ashes  and  placed  in  the 
warm  chamber  until  their  contents  were  at  a  temperature 
of  100°  F.,  when  an  excess  of  sodium  biurate  was  added  to 
each.  The  bottles  were  kept  at  100°  F.  for  five  hours, 
during  which  period  they  were  frequently  agitated.  At  the 
end  of  that  time  the  contents  of  the  bottles  were  filtered 
and  refiltered  through  double  filters  until  perfectly  clear 
filtrates  were  obtained.  The  arnount  of  uric  acid  in 
each  of  the  filtrates  was  then  estimated  by  adding  an 
excess  of  strong  sulphuric  acid,  and  titrating  with  the 
standard  potassium  permanganate  solution  ;  the  quan- 
tity of  uric  acid  found  was  subsequently  calculated 
into  terms  of  sodium  biurate.  The  results  thus  obtained 
are  shown  in  the  following  tables.  The  solubility  of  sodium 
biurate  in  distilled  water  is  placed  at  the  head  of  each  table 
for  comparison. 


174 


GOUT:    INVESTIGATIONS. 


[Part  III. 


TABLE     XVI. 

Showing  the  influence  of  the  mineral  constittients  of  meat  {lean  beef) 
on  the  solubility  of  sodium  biurate  at  ioo°  F. 


Solvent. 


Water 

Water  containing- 
i.o  per  cent,  of  meat  ash     . 
0.5 
0.2 


o.  I 

0.05 

0.02 

O.OI 


Sodium   biurate 
dissolved. 


1 .  10  per   1,000 


0.93 
0.76 
0.56 
0.32 
0.15 

O.  II 

0.85 


From  the  above  table  it  is  seen  that  the  mineral  con- 
stituents of  meat,  in  all  proportions  between  i.o  and  o.oi 
per  cent.,  diminish  the  solvency  of  sodium  biurate.  The 
effect  is  most  marked  when  the  proportions  are  between 
o.i  and  0.02  per  cent.,  which  are  proportions  that  may 
certainly  be  present  in  the  blood  after  eating  a  few  ounces 
of  meat.  It  is  therefore  quite  possible  that  the  well- 
known  influence  of  excessive  meat-eating  on  the  hastening 
or  maturing  of  an  attack  of  gout  may,  in  part  at  least,  be 
due  to  the  action  of  the  mineral  constituents  of  the  meat. 


TABLE    XVII. 

Showing  the  influence  of  the  mineral  constituents  of  milk  on  the  solu- 
bility of  sodium  biurate  at  100°  F. 


Solvent. 


Water 

Water  containing- 
i.o  per  cent,  of  milk  ash 
0.5 
0.2 


0.1 
0.05 
0.02 
0.01 


Sodium   biurate 
dissolved. 


1 .  10  per   1,000 

0.62 

0.58 

0.49 

0.44 

0.72 

0.90  ,, 

0.94 


Chap.  X.] 


VEGETABLE  ASHES. 


175 


The  foregoing  table  shows  that  the  mineral  consti- 
tuents of  milk  in  all  proportions  diminish  the  solvency 
of  sodium  biurate.  The  effect  is  most  marked  when  o.i 
per  cent,  of  milk  ash  is  present.  It  is  extremely  unlikely 
that  such  a  proportion  could  be  present  in  the  blood  un- 
less a  person  were  exclusively  fed  for  some  time  on  milk. 
To  introduce  o.i  per  cent,  of  the  mineral  constituents 
of  milk  into  the  blood  would  require  that  all  the  mineral 
constituents  of  about  twenty-two  ounces  of  milk  should 
be  introduced  at  one  moment  into  the  blood  of  an  adult 
of  average  weight.  These  experiments  therefore  seem 
to  indicate  that  the  mineral  constituents  of  milk  can  exer- 
cise no  appreciable  influence  in  hastening  or  maturing  an 
attack  of  gout. 

TABLE    XVIII. 

Showing  the  influence  of  the  mineral  constituents  of  vegetables  {potatoes, 
spinach,  and  beans)  on  the  solubility  of  sodium  biurate  at  100°  F. 


seven..                                              ^tTjiT' 

Water 

T  .  10  Der   1. 000 

Water  containing — 
i.o  per  cent,  of  vegetable  ash 

0.5 

0.2              ,,                 ,, 

O.I 

0.05 
0.02 

O.OI                 ,, 

2.15 
1.70 
1-35 
1. 15 
1. 10 
1. 10 
1. 10 

From  Table  XVI I L  it  is  seen  that  the  mineral  consti- 
tuents of  vegetables  in  quantities  of  0.1  per  cent,  and 
above  very  appreciably  increase  the  solvency  of  sodium 
biurate.  In  quantities  below  0.1  per  cent,  the  solutions 
exercise  the  same  solvent  power  on  the  biurate  as  distilled 
water.  These  experiments  indicate  that  the  mineral  con- 
stituents of  vegetables,  if  taken  in  sufficient  quantities, 
would  increase  the  solvency  of  sodium  biurate,  and  would 
also  exert  a  solvent  effect  on  gouty  deposits. 


176  GOUT:    INVESTIGATIONS.  [Partiii. 

From  the  results  of  these  prehminary  experiments 
it  appears  probable  that  if  the  mineral  constituents  of 
vegetables  were  present  in  sufficient  quantities  in  the  fluids 
of  a  gouty  person,  they  would  not  only  increase  the  solu- 
bility of  the  sodium  biurate  present  in  these  fluids,  but 
would  also,  by  their  increased  solvent  effects  on  uratic 
deposits,  facilitate  the  removal  of  the  latter.  I  have 
therefore  carried  out  a  long  series  of  experiments  with 
the  mineral  constituents  of  all  the  vegetables  in  ordinary 
use,  in  order  to  elucidate  the  two  following  points  : — (i) 
The  relative  effects  exerted  by  the  mineral  constituents 
of  various  vegetables  on  the  solubility  of  sodium  biurate 
at  the  temperature  of  the  human  body,  and  therefore 
presumably  on  uratic  deposits  ;  and  (2)  the  influence, 
if  any,  exerted  by  these  constituents  in  retarding 
the  conversion  of  the  sodium  quadriurate  into  the 
sodium  biurate.  Obviously  the  elucidation  of  these 
points  would  have  a  material  bearing  on  the  treatment 
of  gout.* 

The  solvent  effects  exerted  by  the  mineral  con- 
stituents of  various  veg-etables  on  sodium  biurate. 
— The  method  of  carrying  out  these  experiments  was 
similar  to  that  previously  described.  I  operated  separately 
on  the  mineral  constituents  of  certain  vegetables,  viz. 
Spinach,  Brussels  sprouts,  potato,  asparagus.  Savoy  cab- 
bage, French  beans,  lettuce,  beetroot,  winter  cabbage, 
celery,  turnip  tops,  turnip,  carrot,  cauliflower,  seakale, 
and  green  peas.  The  results  obtained  are  shown  in  the 
following  sixteen  tables,  which  are  arranged  in  the  order 
of  the  average  solvent  effect  exerted  by  the  mineral  con- 
stituents of  the  various  vegetables,  commencing  with 
those  exercising  the  greatest  influence.  The  solubihty 
of  sodium  biurate  in  distilled  water  is  placed  at  the  head 
of  each  table  for  comparison. 

*  The  results  of  these  experiments  were  first  communicated  to  the  Royal 
Medical  and  Chirurgical  Society  of  London  in  a  paper  read  on  June  14th,  189S. 


Chap.  X.J 


VEGETABLE    ASHES. 


177 


TABLE    XIX. 

Showing  the  infltience  of  the  mineral  constituents  of  spinach  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

1 .  10 

per  1,000 

1 . 0  per 

Water  containing — 
cent,  of  spinach  ash       .... 

.S..36 

0.5 

2.76 

0.2 

2.  12 

0. 1 

I  .90 

0.05 

1.52 

0.02 

I. 21 

O.OI 

I. 18 

TABLE    XX. 

Showing  the  influence  of  the  mineral  constituents  of  Brussels  sprouts 
on  the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Water 

Water  containing — ■ 
i.o  per  cent,  of  Brussels  sprouts  ash 

0.5 
0.2 
o.  I 
0.05 
0.02 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per   1,000 


3.06 
2.21 
1.68 
1 .62 
1.52 
1.30 
1.23 


TABLE    XXI. 

Showing  the  influence  of  the  mineral  constituents  of  potato  on   the 
solubility  of  soditim  biurate  at  100°  F. 


Solvent. 


Water 

Water  containing- 
i.o  per  cent,  of  potato  ash 
0.5 
0.2 
o.  I 
0.05 
0.02 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per   1,000 


2.49 

2. 17 

92 

47 
36 
12 
10 


178 


GOUT:    INVESTIGATIONS. 


[Part  III. 


TABLE     XXII. 

Showing  the  influence  of  the  mineral  constituents  of  asparagus  on  the 
solubility  of  sodium  hiurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

1 .  10 

2.77 
2.09 
1.58 
1.45 

1-33 
1. 12 
1 .10 

per  1,000 

Water  containing — 
1.0  per  cent,  of  asparagus  ash  . 

0.5 

0.2 

0.1 

0.05             ,,                  ,, 

0.02             ,,                  ,, 

0.01             ,,                  ,, 

TABLE    XXIII. 

Showing  the  influence  of  the  mineral  constituents  of  Savoy  cabbage  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 

dissolved. 

Water 

I  .  10 

per  1,000 

Water  containing — 

1.0  per  cent,  of  Savoy  cabbage  ash     . 

2.32 

0.5 

92 

0.2 

77 

0.1 

S7 

0.05 

34 

0.02               ,,                      ,, 

13 

0.01 

ID 

TABLE    XXIV. 

Showing  the  influence  of  the  mineral  constituents  of  French  beans  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

I.  ID 

2.48 
1.87 
1.68 
1.56 
1.28 
1. 16 
1. 10 

per  1,000 

Water  containing— 
1.0  per  cent,  of  French  beans  ash 

0.5 

0.2 

0.1 

0.05 

0.02 

o.oi              ,,                     ,, 

Chap,  X.] 


VEGETABLE  ASHES. 


179 


TABLE    XXV. 

Showing  the  influence  of  the  mineral  constituents  of  lettuce  on   the 
solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Water 

Water  containing- 
i.o  per  cent,  of  lettuce  ash 
0.5 
0.2 
o.  I 
0.05 
0.02 

O.OI 


Sodium  biurate 
dissolved. 


I  .  10  per   1,000 


.72 
.92 
•57 
•53 
.21 

.  ID 
.09 


TABLE    XXVI. 

Showing  the  influence  of  the  mineral  constituents  of  beetroot  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

Water  containing — 
i.o  per  cent,  of  beetroot  ash     .... 

I  .  10 
2.46 

per   1,000 

0.5 
0.2 

82 
60 

0.1 

0.05 

0.02 

45 
34 
15 

O.OI 

10 

TABLE    XXVII. 

Showing  the  influence  of  the  mineral  constituents  of  winter  cabba^ 
on  the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

Water  containing — 
1.0  per  cent,  of  cabbage  ash 

0.5 

0.2 

0.1 

0.05 

0.02 

O.OI                   „ 

1 .  10 

2.30 
2.14 
1.63 

I-3I 
1.23 
1 .  10 
1 .  10 

per  1,000 

GOUT:    INVESTIGATIONS. 


[Part  III. 


TABLE    XXVIII. 

Showing  the  inflvience   of  the   mineral  constituents   of  celery   on   the 
solubility  of  sodium  biurate  at  ioo°  F. 


Solvent. 


Water 

Water  containing- 
o  per  cent,  of  celery  ash    . 

5 

2 


I 
O 

o 

O.  I 

0.05 

0.02 

O.OI 


Sodium  biurate 

dissolved. 

I  .  10 

per  1,000 

2.20 

1.84 

1-53 

1.44 

1.30 

1 .  10 

1 .06 

TABLE    XXIX. 

Showing  the  influence  of  the  mineral  constituents  of  turnip  tops  on 
the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Water 

Water  containing — - 
i.o  per  cent,  of  turnip  tops  ash 
0.5 
0.2 
o.  I 
0.05 
0.02 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per   1,000 

2.16 

1.82 

1.58 

1.42  ,, 

1.20 

I -13 
I .  II 


TABLE    XXX. 

Showing  the  influence  of  the  mineral  constituents  of  turnips  on  the 
solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Sodium  biurate 
dissolved 


Water 

Water  containing- 
i.o  per  cent,  of  turnip  ash  . 
0.5 


0.2 
o.  I 
0.05 
0.02 

O.OI 


1 .  10  per   1,000 

2.04 

1.78 
1.50 
1.42 
1-32 
1. 14 


Chap.  X.] 


VEGETABLE  ASHES. 


I5I 


TABLE    XXXI. 

Showing   the   influence   of  the   mineral  constituents   of  carrot   on   the 
solubility  of  sodium  biurate  at  ioo°  F. 


Sodium  biurate 
dissolved. 


Solvent. 

Water 

Water  containing— 

I .  o  per 

cent,  of  carrot  ash 

0.5 

0.2 

0. 1 

0.05 

0.02 

O.OI 

1 .  10  per  1,000 


63 
53 
47 
45 
3?) 
13 
II 


TABLE    XXXIL 

Showing  the  influence  of  the   mineral   constituents   of  cauliflower  on 
the  solubility  of  sodium  biurate  at  100^  F. 


Solvent. 


Water 

Water  containing — • 
i.o  per  cent,  of  cauliflower  ash 

0.5 
0.2 
o.  I 
0.05 
0.02 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per  1,000 


52 
50 
42 

34 
28 
09 
09 


TABLE    XXXIII. 

Showing  the  influence  of  the  mineral  constituents  of  seakale  on  the 
solubility  of  sodium  bivirate  at  100°  F. 


Solvent. 

Sodium  biurate 
dissolved. 

Water 

1 .  10  per   1,000 
1-49 

Water  containing — 
1.0  per  cent,  of  seakale  ash 

0.5 

1-47 

0-2 

1-35 

o-i 

1-23 

0.05 

1 .  10 

0-02 

1 .  10 

O.OI 

1. 10 

l82 


GOUT:    INVESTIGATIONS. 


[Part  IIL 


TABLE    XXXIV. 

Showing  the  influence  of  the  mineral  constituents  of  green  peas  on  the 
solubility  of  sodium  hiurate  at  ioo°  F. 


Solvent. 


Water 

Water  containing — 
i.o  per  cent,  of  green  peas  ash 

0.5 

0.2 

o.  I 

0.0s 

0.02  ,, 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per   1,000 


0.99 
1 .01 
1 .04 
1 .  10 
1 .  10 
1 .  10 
1. 10 


From  the  results  detailed  in  these  tables  it  is  evident 
that  0.05  per  cent,  and  over  of  the  mineral  constituents 
of  nearly  all  the  vegetables  very  appreciably  increases 
the  solubility  of  sodium  biurate.  The  solitary  exception 
is  in  the  case  of  the  mineral  constituents  of  green  peas, 
which  practically  exert  no  influence  whatever  on  the 
solubility  of  the  biurate. 

As  I  considered  that  these  solvent  effects  of  the  mineral 
constituents  of  most  vegetables  on  the  biurate  might  have 
some  bearing  on  the  treatment  of  gout,  I  next  en- 
deavoured to  ascertain  whether  these  effects  were  due  to 
the  alkalinity  of  the  vegetables  ashes,  or  whether  they 
could  be  referred  to  any  one  saline  constituent  of  the 
vegetables. 

Experimental  proof  that  the  solvent  effects  of  the 
mineral  constituents  of  vegetables  on  sodium  biurate 
are  not  due  to  their  degree  of  alkalinity. — That  the 
solvent  effect  exerted  respectively  by  the  mineral  consti- 
tuents of  each  vegetable  on  the  sodium  biurate  was  not 
proportional  to  the  alkalinity  of  the  ash  was  very  easily 
determined.  I  made  estimations  of  the  alkalinities  of 
the  different  vegetable  ashes,  and  calculated  the  percentages 
of  alkalinity  in  terms  of  sodium  carbonate.     The  alkalinity 


Chap.  X.] 


VEGETABLE  ASHES. 


183 


of  the  ashes  was  due  to  potassium  and  sodium  carbonates  ; 
none  of  the  ashes  contained  either  potassium  or  sodium 
hydrate.  The  following  table  shows  a  comparison  of  the 
solubility  exerted  by  the  mineral  constituents  of 
vegetables  on  sodium  biurate,  and  the  alkalinity 
of  those  constituents  : — 

TABLE    XXXV. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  rnineyal  con- 
stituents of  vegetables  is  not  dependent  on  the  alkalinity  of  those 
constituents. 


Vegetables  arranged  in 
order  of  solvent  effect 
of  their  mineral  con. 
stituents  on  sodium 
biurate.  Commenc- 
ing with  those  exert- 
ing the  greatest  effect. 


Spinach 

Brussels  sprouts 
Potato 
Asparagus 
Savoy  cabbage 
French  beans 
Lettuce 
Beetroot 
Cabbage 
Celery- 
Turnip  tops 
Turnip 
Carrot 
Cauliflower 
Seakale 
Green  peas 


Vegetables  arranged  in  order  of  the  alkalinity  of 
their  ashes,  and  showing  percentages  of  alkalinity- 
reckoned  as  sodium  carbonate.  Commencing  with 
the  most  alkaline. 


Spinacli 26.00 

Celery 20.80 

Turnip 20.80 

Potato 17-55 

Beetroot 1 5  •  60 

Cauliflo-wer 13-20 

Carrot 1 3  -  00 

Brussels  sprouts 12.35 

French  beans     12.35 

Turnip  tops 1 1 .  70 

Lettuce ir.05 

Asparagus 8-45 

Cabbage 5-85 

Green  peas 5  •  20 

Savoy  cabbage 4-55 

Seakale 1.95 


It  is  evident  from  a  glance  at  this  table  that  the  solvent 
effect  of  a  vegetable  ash  on  sodium  biurate,  with  the  ex- 
ception of  spinach  ash,  bears  no  relationship,  either  of  a 
direct  or  an  inverse  ratio,  to  the  alkalinity  of  the  ash. 
For  instance,  it  can  be  seen  that  the  solvent  effect  on  the 
biurate  of  the  ash  of  Brussels  sprouts  is  high,  while  its 


i84  GOUT:    INVESTIGATIONS.  [partHl 

alkalinity  is  low  ;  on  the  other  hand,  the  solvent  effect 
on  the  biurate  of  the  ash  of  celery  is  low,  while 
its  alkalinity  is  high.  In  other  words,  it  is  evident 
that  the  order  in  which  the  vegetables  are  arranged 
as  regards  the  solvent  effect  of  the  mineral  constitu- 
ents .  on  the  biurate  is  neither  the  order  nor  the 
inverse  order  of  their  relative  alkalinities.  These 
results  support  the  conclusions  I  arrived  at  from 
some  experiments  made  with  blood  serum,  and  described 
in  the  "  Goulstonian  Lectures  "  of  1897.  I  then  showed 
that  a  diminution  in  the  alkalinity  of  blood  serum  did 
not  cause  a  diminution  in  the  solvent  power  of  the  serum 
for  biurate,  and,  conversely,  that  an  increase  in  the  alka- 
linity of  the  serum  did  not  increase  its  solvent  power  for 
the  biurate. 

Experimental  proof  that  the  solvent  effects  of  the 
mineral  constituents  of  vegetables  on  sodium  biurate 
are  not  due  to  any  single  constituent.  —  The  next 
problem  to  solve  was  whether  the  effect  exerted  by 
the  mineral  constituents  of  vegetables  in  increasing 
the  solubility  of  sodium  biurate  is  due  to  any 
one  constituent.  With  regard  to  this  point,  it 
appeared  probable  beforehand  that  such  would  not 
prove  to  be  the  case,  since  Sir  William  Roberts 
had  shown  that  sodium,  calcium,  and  magnesium 
salts  diminish  the  solvent  power  of  water  on  sodium 
biurate,  and  that  potassium  salts  exercise  no  influ- 
ence, one  way  or  the  other,  on  the  solubility  of  the 
biurate. 

Now  it  can  easily  be  demonstrated  that  the  solvent 
effect  is  not  due  to  the  potassium  salts.  The  next 
table  contains  a  comparison  of  the  solvent  powers 
exerted  by  the  mineral  constituents  of  vegetables  on 
sodium  biurate,  and  the  proportions  of  potassium  salts 
present. 


C..AP.X.]    POTASSIUM    SALTS    IN    VEGETABLES.       185 


TABLE    XXXVI. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  mineral  con- 
stituents of  vegetables  is  not  dependent  on  the  amounts  of  potassium 
salts  present. 


Vegetables  arranged  in 

order  of  solvent  effect 

Vegetables  arranged  in  order  of  the  proportions  of 

of  their  mineral  con- 

potassium   salts    present,    and    showing    tlie 

)er- 

stituents    on    sodium 

centages  of  potassium  salts  present  in   the  ashes, 

biurate.       Commenc- 

reckoned as  potassium  oxide.     Commencing  with 

ing  with  those  exert- 

those richest  in  potassium  salts. 

ing  the  greatest  effect. 

Spinach 

Potato 56 

03 

Brussels  sprouts 

Turnip 

•      54 

05 

Potato 

Carrot 

53 

2^ 

Asparagus 

Lettuce    . 

.     48 

01 

Savoy  cabbage 

French  beans 

- 

46 

50 

French  beans 

Asparagus 

39 

21 

Lettuce 

Green  peas    . 

38.96 

Beetroot 

Beetroot  . 

38 

22 

Cabbage 

Cabbage  . 

27 

71 

Celery 

Brussels  sprouts 

35 

00 

Turnip  tops 

Celery 

23 

14 

Turnip 

Turnip  tops  . 

30 

55 

Carrot 

Savoy  cabbage 

26 

82 

Cauliflower 

Cauliflower    . 

^2 

46 

Seakale 

Spinach    . 

23 

43 

Green  peas 

Seakale    . 

2 

59 

It  is  evident  from  this  table  that  the  solvent  effect 
of  the  mineral  constituents  of  vegetables  on  sodium  biurate 
bears  no  relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  proportions  of  potassium  salts  present.  For  in- 
stance, it  can  be  seen  that  the  solvent  effect  on  the  biurate 
of  the  ash  of  spinach  is  high,  while  the  proportion  of  potas- 
sium salts  is  low  ;  on  the  other  hand,  the  solvent  effect 
on  the  biurate  of  the  ash  of  turnips  is  low,  while  the  pro- 
portion of  potassium  salts  is  high. 

It  can  also  be  demonstrated  that  the  increased  solubility 
of  the  biurate  effected  by  the  mineral  constituents  of 
vegetables  is  not  due  to  the  sodium  salts.  Table  XXXVII. 
contains  a  comparison  of  the   solvent  powers  exerted  by 


i86 


GOUT:    INVESTIGATIONS. 


[Part  III. 


the  mineral  constituents  of  vegetables  on  sodium  biurate, 
and  the  proportions  of  sodium  salts  present. 

TABLE    XXXVII. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  mineral  con- 
stituents of  vegetables  is  not  dependent  on  the  amounts  of  sodium 
salts  present. 


Vegetables  arranged  in 
order  of  solvent  effect 
of  their  mineral  con- 
stituents on  sodium 
biurate.  Commenc- 
ing with  those  exert- 
ing the  greatest  effect. 


Spinach 

Brussels  sprouts 

Potato 

Asparagus 

Savoy  cabbage 

French  beans 

Lettuce 

Beetroot 

Cabbage 

Celery 

Turnip  tops 

Turnip 

Carrot 

Cauliflower 

Seakale 

Green  peas 


Vegetables  arranged  in  order  of  the  proportions  of 
sodium  salts  present,  and  showing  the  percentages 
of  sodium  salts  present  in  the  ashes,  reckoned  as 
sodium  oxide.  Commencing  with  those  richest 
in  sodium  salts. 


Seakale 33-84 

Spinach 3 1  •  42 

Beetroot 31 -17 

French  beans     30.50 

Celery 19-33 

Asparagus 16.79 

Carrot 14 -17 

Savoy  cabbage 13-86 

Brussels  sprouts 12.60 

Lettuce 1 1 .  80 

Cauliflower 10.87 

Turnip 6- 37 

Green  peas 5  -  20 

Turnip  tops 4- 19 

Cabbage 2.39 

Potato 2.18 


This  table  shows  that  the  solvent  effect  of  the  mineral 
constituents  of  vegetables  on  sodium  biurate  bears  no 
relationship,  either  of  a  direct  or  an  inverse  ratio,  to 
the  proportions  of  sodium  salts  present.  For  instance, 
it  can  be  seen  that  the  solvent  effect  on  the  biurate  of 
the  ash  of  potato  is  high,  while  the  proportion  of  sodium 
salts  is  low  ;  on  the  other  hand,  the  solvent  effect  on  the 
biurate  of  the  ash  of  seakale  is  low,  while  the  proportion 
of  sodium  salts  is  high. 

In  like  manner  it  can  be  demonstrated  that  the  increased 
solubility  of  the  biurate  effected  by  the  mineral  constituents 


chap.x.]    calcium  salts  in  vegetables. 


187 


of  vegetables  is  not  due  to  the  calcium  salts.  The  following 
table  contains  a  comparison  of  the  solvent  powers  exerted 
by  the  mineral  constituents  of  vegetables  on  sodium  biurate, 
and  the  proportions  of  calcium  salts  present  : — 

TABLE    XXXVIII. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  mineral  con- 
stituents of  vegetables  is  not  dependent  on  the  amounts  of  calcium 
salts  present. 


Vegetables  arranged  in 
order  of  solvent  effect 
of  their  mineral  con- 
stituents on  sodium 
biurate.  Commenc- 
ing with  those  exert- 
ing the  greatest  effect. 


Spinach 

Brussels  sprouts 

Potato 

Asparagus 

Savoy  cabbage 

French  beans 

Lettuce 

Beetroot 

Cabbage 

Celery 

Turnip  tops 

Turnip 

Carrot 

Cauliflower 

Seakale 

Green  peas 


Vegetables  arranged  in  order  of  the  proportions  of 
calcium  salts  present,  and  showing  the  percentages 
of  calcium  salts  present  in  the  ashes,  reckoned  as 
calcium  oxide.  Conunencing  with  those  richest 
in  calcium  salts. 


Turnip  tops 37  •  1 5 

Seakale 27.56 

Cauliflower 23.33 

French  beans      17-48 

Cabbage 17 -14 

Lettuce 15.02 

Savoy  cabbage 14-83 

Turnip 13.38 

Celery 13 -06 

Spinach 10.64 

Carrot 6.88 

Brussels  sprouts 6.16 

Potato      ........  5.46 

Asparagus S-^S 

Green  peas 4-98 

Beetroot 2.58 


It  is  clear  from  this  table  that  the  solvent  effect 
of  the  mineral  constituents  of  vegetables  on  sodium  biurate 
bears  no  relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  proportions  of  calcium  salts  present.  For  instance, 
it  can  be  seen  that  the  solvent  effect  on  the  biurate  of  the 
ash  of  potato  is  high,  while  the  proportion  of  calcium  salts 
is  low  ;  on  the  other  hand,  the  solvent  effect  on  the  biurate 
of  the  ash  of  seakale  is  low,  while  the  proportion  of  calcium 
salts  is  high. 

Similarly  it  can  be  shown  that  the  increased  solvent 


GOUT:    INVESTIGATIONS. 


[Part  III. 


effect  on  the  biurate  exerted  by  the  mineral  constituents 
of  vegetables  is  not  due  to  either  the  magnesium  or  iron 
salts  present. 

It  can  also  be  demonstrated  that  the  increased  solu- 
bility of  the  biurate  is  not  due  to  the  phosphates  present 
in  the  vegetables.  The  following  table  contains  a  com- 
parison of  the  solvent  powers  exerted  by  the  mineral  con- 
stituents of  vegetables  on  sodium  biurate,  and  the  pro- 
portions of  phosphates  present : — 

TABLE    XXXIX. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  mineral  con- 
stittients  of  vegetables  is  not  dependent  on  the  amounts  of  phos- 
phates present. 


Vegetables  arranged  in 

order  of  solvent  effect 

Vegetables  arranged  in  order  of  the  proportions  of 

of  their  mineral  con- 

phosphates present,  and  showing  the  percentages 

stituents    on    sodium 

of  phosphates  present  in  the  ashes,  reckoned  as 

biurate.       Commenc- 

phosphoric   anhydride.     Commencing    with    those 

ing  with  those  exert- 

richest in  phosphates. 

ing  the  greatest  effect. 

Spinach 

Green  peas 35-62 

Brussels  sprouts 

Cauliflower    . 

22.  14 

Potato 

Asparagus 

21.93 

Asparagus 

Potato      .      . 

15-99 

Savoy  cabbage 

Carrot 

15.02 

French  beans 

Celery 

14-39 

Lettuce 

Brussels  sprouts 

14.20 

Beetroot 

Savoy  cabbage 

13-19 

Cabbage 

French  beans 

12.21 

Celery 

Cabbage  . 

11.99 

Turnip  tops 

Lettuce    . 

9.62 

Turnip 

Turnip 

9.26 

Carrot 

Spinach    . 

8.56 

Cauliflower 

Beetroot  . 

8.25 

Seakale 

Seakale     . 

8.00 

Green  peas 

Turnip  tops  . 

6.15 

It  is  manifest  from  this  table  that  the  solvent  effect 
of  the  mineral  constituents  of  vegetables  on  sodium  biurate 
bears  no  relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  proportions  of  phosphates  present.  For  instance, 
it  can  be  seen  that  the  solvent  effect  on  the  biurate  of  the 


ClIAP.  X.] 


SULPHATES    IN    VEGETABLES. 


189 


ash  of  spinach  is  high,  while  the  proportion  of  phosphates 
is  low  ;  on  the  other  hand,  the  solvent  effect  on  the  biurate 
of  the  ash  of  green  peas  is  low,  while  the  proportion  of 
phosphates  is  high. 

It  can  also  be  demonstrated  that  the  increased  solu- 
bility of  the  biurate  is  not  due  to  the  sulphates  present 
in  the  vegetables.  The  following  table  contains  a  com- 
parison of  the  solvent  powers  exerted  by  the  mineral 
constituents  of  vegetables  on  sodium  biurate,  and  the 
proportions  of  sulphates  present : — 

TABLE    XL. 

Showing  that  the  solvent  effect  on  sodium  hiurate  of  the  mineral  con- 
stituents of  vegetables  is  not  dependent  on  the  amounts  of  sulphates 
present. 


Vegetables   arranged  in 

order  of  solvent  effect 

Vegetables  arranged  in 

order  of  the  proportions  of 

of  their  mineral  con- 

sulphates   present,    and    showing   the    percentages 

stituents    on    sodium 

of    sulphates    present 

in    the   ashes,   reckoned   as 

biurate.       Commenc- 

sulphuric    anhydride. 

Commencing     with     those 

ing  with  those  exert- 

richest in  sulphates. 

ing  the  greatest  effect. 

Spinach 

Seakale    . 

19-78 

Brussels  sprouts 

Turnip  tops 

15.27 

Potato 

Cauliflower    . 

14. 16 

Asparagus 

Savoy  cabbage  . 

12.85 

Savoy  cabbage 

Turnip 

12.47 

French  beans 

Brussels  sprouts 

8.31 

Lettuce 

Cabbage  . 

7.28 

Beetroot 

French  beans 

6.82 

Cabbage 

Potato      .      .      . 

5.60 

Celery- 

Asparagus 

5 -40 

Turnip  tops 

Carrot 

5.20 

Turnip 

Spinach    .      . 

4.44 

Carrot 

Green  peas    . 

4-36 

Cauliflower 

Lettuce    . 

3-92 

Seakale 

Beetroot 

2.41 

Green  peas 

Celery 

1. 10 

This  table  makes  it  evident  that  the  solvent  effect  of 
the  mineral  constituents  of  vegetables  on  sodium  biurate 
bears  no  relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  proportions  of  sulphates  present.     For  instance,  it 


igo 


GOUT:    INVESTIGATIONS. 


[Part  III. 


can  be  seen  that  the  solvent  effect  on  the  biurate  of  the  ash 
of  spinach  is  high,  while  the  proportion  of  sulphates  is  low  ; 
on  the  other  hand,  the  solvent  effect  on  the  biurate  of  the  ash 
of  seakale  is  low,  while  the  proportion  of  sulphates  is  high. 

Finally,  as  disposing  of  all  the  mineral  constituents 
of  any  importance  in  vegetables,  it  can  be  demonstrated 
that  the  increased  solubility  of  the  biurate  is  not  due  to 
the  chlorides  present  in  the  vegetables,  as  seen  in  the 
following  table  : — 

TABLE    XLI. 

Showing  that  the  solvent  effect  on  sodium  biurate  of  the  mineral  con- 
stituents of  vegetables  is  not  dependent  on  the  amounts  of  chlorides 
present. 


Vegetables  arranged  in 
order  of  solvent  effect 
of  their  mineral  con- 
stituents on  sodium 
biurate.  Commenc- 
ing with  those  exert - 


Vegetables  arranged  in  order  of  the  proportions  of 
chlorides  present,  and  showing  the  percentages  of 
chlorides  present  in  the  ashes,  reckoned  as  chlorine. 
Commencing  with  those  richest  in  chlorides. 


ing  the  greatest  effect. 

Spinach 

Celery 22.14 

Brussels  sprouts 

Beetroot 

18.13 

Potato 

Seakale    . 

15.46 

Asparagus 

Cabbage  . 

9.09 

Savoy  cabbage 

Lettuce    . 

8.80 

French  beans 

Spinach    . 

7.78 

Lettuce 

Savoy  cabbage 

7-53 

Beetroot 

Turnip  tops 

7-3Z 

Cabbage 

Asparagus 

6.62 

Celery 

Turnip 

5.06 

Turnip  tops 

Cauliflower    . 

4-83 

Turnip 

Carrot 

3-70 

Carrot 

Brussels  sprouts 

3.00 

Cauliflower 

Potato      .      . 

2.50 

Seakale 

French  beans 

2.50 

Green  peas 

Green  peas    , 

2. 10 

From  this  table  it  is  clear  that  the  solvent  effect  of 
the  mineral  constituents  of  vegetables  on  sodium  biurate 
bears  no  relationship,  either  of  a  direct  or  an  inverse  ratio, 
to  the  proportions  of  chlorides  present.  For  instance,  it 
can  be  seen  that  the  solvent  effect  on  the  biurate  of  the 


chap.x]  artificial    and    natural    ash.      191 

ash  of  Brussels  sprouts  is  high,  while  the  proportion  of 
chlorides  is  low  ;  on  the  other  hand,  the  solvent  effect 
on  the  biurate  of  the  ash  of  seakale  is  low,  while  the  propor- 
tion of  chlorides  is  high. 

These  results  collectively  show  that  the  solvent  effect 
exerted  on  sodium  biurate  by  the  mineral  constituents  of 
vegetables  is  not  due  to  any  one  constituent. 

Experimental  proof  that  an  artificially  prepared  ash 
does  not  react  to  sodium  biurate  in  the  same  manner 
as  a  natural  vegretable  ash.— I  next  endeavoured  to 
ascertain  whether  an  artificially  prepared  ash  of  the  same 
composition  as  the  natural  ash  of  one  of  the  vegetables 
would  exercise  a  similar  effect  in  increasing  the  solubility 
of  the  sodium  biurate  to  that  possessed  by  the  natural 
ash.  For  this  purpose  I  selected  the  spinach  ash,  which 
has  the  greatest  solvent  effect  on  the  biurate.  An  artificial 
ash  was  prepared,  which  was  made  with  the  same  propor- 
tions of  potassium,  sodium,  calcium,  sulphates,  phosphates 
and  chlorides  as  those  present  in  the  natural  spinach  ash, 
and  also  of  precisely  the  same  degree  of  alkalinity.  Ex- 
periments were  carried  out  with  this  artificial  ash  and  the 
biurate  in  a  similar  manner  to  that  employed  in  working 
with  the  natural  vegetable  ashes.  The  following  table 
shows  the  results  of  these  experiments  : — ■ 
TABLE    XLII. 

Showing  the  influence  of  artificial  spinach  ash  on  the  solubility  of 
sodium  biurate  at  100''  F. 


Solvent. 


Water 

Water  containing — 
i.o  per  cent,  of  artificial  spinach  ash 
0.5 

0-2 
0.1 

0-05 

0.02  „ 

O.OI 


Sodium  biurate 
dissolved. 


1 .  10  per  1,000 


0.20 

0.34 
0.62 
0.86 
0.96 
1 .04 
1 .06 


192 


GOUT:    INVESTIGATIONS. 


[Part  III. 


These  results  are  very  remarkable,  as  they  indicate 
that  the  artificial  ash  exercises  in  all  proportions  a  deterrent 
effect  on  the  solubility  of  the  biurate.  This  deterrent 
effect  is  well  seen  by  contrasting  the  results  with  those  of 
the  natural  ash,  which  show  the  marked  solvent  effect 
exerted  by  the  latter  on  the  biurate. 

TABLE    XLIII. 

Shoiving  the   different  influences  exerted  by  artificial  and  by  natural 
spinach  ashes  on  the  solvency  of  the  biurate  at  100°  F. 


Solvent. 


Water 


Water  containing- 
i.o  per  cent,  of  ash 

0.5 

0.2 

0.1 

0.05 

0.02 

O.OI 


Sodium  biurate  dissolved  in  1,000  parts. 


Artificial  spinach  ash. 


0.20 

0.34 
0.62 
0.86 
0.96 
1 .04 
1 .06 


Natural  spinach  ash. 


2.76 
2. 12 
1 .90 
1.52 
1 .21 
1. 18 


The  only  explanation  that  I  can  offer  of  these  remark- 
able results  is  that  in  the  natural  ash  there  is  some  com- 
bination of  the  mineral  constituents  which  cannot  be  arti- 
ficially imitated,  and  that  upon  this  natural  combination 
of  the  salts  is  dependent  the  increased  solvent  effect  exerted 
on  the  biurate  by  the  mineral  constituents  of  most  vege- 
tables. If  this  view  be  correct,  then  modern  science  is 
but  confirming  the  correctness  of  the  practice  of  those 
ancients  who  employed  vegetable  ashes  in  the  treatrhent 
of  gout. 

It  is  well  to  make  here  a  brief  reference  to  the  experi- 
ments previously  described,  which  show  that  the  mineral 
constituents  of  meat  exercise  a  marked  deterrent  effect 
on  the  solubility  of  sodium  biurate  ;    and  that  this  effect 


Chap.  X.] 


VEGETABLES    AND    GOUT. 


193 


is  most  marked  by  proportions  of  the  mineral  constituents 
which  may  certainly  be  present  in  the  blood  after  eating 
a  few  ounces  of  meat.  The  following  table  shows  in  con- 
trast the  effects  exercised  respectively  by  the  mineral 
constituents  of  lean  beef  and  spinach  on  the  solubility  of 
the  biurate. 

TABLE    XLIV. 

Showing  the  respective  effects  exercised  by  the  mineral  constituents  of 
beef  and  spinach  on  the  solubility  of  sodium  biurate  at  100°  F. 


Solvent. 


Sodium  biurate  dissolved  in  1,000  parts. 


Water 


Water  containing- 
i.o  per  cent,  of  ash 

0.5 

0.2 

0.1 

0.05 

0.02 

o.oi 


Expepimental  inquiry  to  ascertain  the  effect  exerted 
by  the  mineral  constituents  of  various  veg-etables 
on  the  conversion  of  sodium  quadriurate  into  sodium 
biurate. — It  is  well  known  from  the  researches  of 
Bence  Jones  and  of  Sir  William  Roberts  that  sodium 
quadriurate  is  an  unstable  body,  and  is  gradually  converted 
by  combination  with  the  sodium  carbonate  of  the  blood 
into  sodium  biurate,  which  latter  body,  on  account  of  its 
comparative  insolubility,  deposits  in  the  tissues  and  thus 
constitutes  the  gouty  uratic  deposit.  This  gradual  con- 
version of  the  quadriurate  into  biurate  is  known  as  the 
maturation  process. 

It  is  obviously  of  therapeutical  importance  to  know 
whether  the  mineral  constituents  of  any  of  the  vegetables, 


194  GOUT:    INVESTIGATIONS.  [Partiii. 

in  addition  to  exerting  an  increased  solvent  effect  on  the 
biurate,  possess  the  power  of  delaying  this  maturation 
process  ;  or,  in  other  words,  of  inhibiting  the  conversion 
of  the  quadriurate  into  the  biurate.  In  order  to  ascertain 
this,  I  conducted  a  series  of  experiments.  In  all  these 
experiments  I  employed  Sir  William  Roberts's  standard 
solution,  as  being  a  more  convenient  medium  to  work  with 
than  blood  serum.  This  standard  solution  contains  0.5 
per  cent,  of  sodium  chloride  and  0.2  per  cent,  of  sodium 
bicarbonate  dissolved  in  distilled  water.  Sir  William 
Roberts  found  that  this  solution  is  a. fairly  exact  represent- 
ation of  blood  serum,  in  so  far  as  its  saline  ingredients  are 
concerned,  and  that  it  reacted  with  uric  acid  and  the 
urates  in  the  same  manner  as  blood  serum  itself,  and  in 
the  same  manner  as  a  solution  comprising  all  the  salines 
of  the  serum  in  their  due  proportions. 

The  experiments  were  conducted  in  the  following  way. 
Pure  sodium  quadriurate  was  prepared  by  shaking  for 
one  minute  ten  grammes  of  uric  acid  with  a  litre  of  a 
boiling-hot  5  per  cent,  solution  of  sodium  acetate.  This 
was  filtered  hot,  and  the  filtrate  was  then  rapidly  cooled 
on  ice.  The  quadriurate,  which  falls  down,  was  at  once 
collected  on  a  filter,  washed  with  absolute  alcohol,  and 
dried  at  100°  F.  Ten  milligrammes  of  pure  sodium  quadri- 
urate were  well  rubbed  with  ten  drops  of  the  standard  solu- 
tion, and  the  mixture  was  placed  in  a  small  corked  bottle 
in  the  warm  chamber  and  kept  at  100°  F.  Every  half- 
hour  a  small  quantity  of  the  mixture  was  examined  under 
a  high  power  of  the  microscope,  and  the  time  at  which 
crystals  of  sodium  biurate  first  appeared  was  noted.  This 
represented  the  time  occupied  by  the  maturation  process 
when  the  standard  solution  was  saturated  with  sodium 
quadriurate.  Similar  experiments  were  conducted  with 
the  same  amount  of  sodium  quadriurate  in  the  same  quan- 
tity of  standard  solution  containing  respectively  o .  i  per 
cent,  of  the  mineral  constituents  of  each  of  the  vegetables 


Chap.  X.] 


VEGETABLES    AND    GOUT. 


195 


in  ordinary  use.     The  results  are  shown  in  the  following 
table  : — 

TABLE    XLV. 

Showing  the  effects  exerted  by  the  mineral  constituents    of   vegetables 
on  the  conversion  of  sodium  quadriurate  into  sodium  biurate. 


Solvent. 

Crystals  of  sodium 
biurate  first  appeared 
in — 

Standard  solution '     . 

2   hours 

Standard  solution  containing — 

0. 1  per  cent. 

of  potato  ash 

cauliflower  ash     . 

2 
2 

lettuce            ,, 

2 

carrot             ,, 

2 

asparagus 
beetroot 

2|-       , 

3       . 

green  peas    ,, 

celery 

Brussels  sprouts  ash 

cabbage 

turnip  tops 

turnip 

Savoy  cabbage    ,, 

seakale 

3h     . 
l\     . 
4 

4       , 
4       , 
4       . 
4 
4 

French  beans 

4i     , 

spinach                   ,, 

5       . 

These  results  show  that  the  mineral  constituents  of 
some  of  the  vegetables — notably  spinach,  Brussels  sprouts, 
French  beans,  cabbage,  turnip  tops,  and  turnips — very 
considerably  delay  the  conversion  of  sodium  quadriurate 
into  sodium  biurate.  The  inference  is  that  if  such  mineral 
constituents  were  present  in  suitable  proportions  in  the 
blood  of  gouty  subjects,  the  elimination  of  that  body 
might  be  secured  without  the  occurrence  of  any  precipi- 
tation of  the  biurate  in  the  tissues.  Moreover,  it  must  be 
borne  in  mind  that  these  experiments  were  conducted 
under  very  stringent  conditions,  in  that  they  were  all 
carried  out  with  a  saturated  solution  of  the  quadriurate, 
and  it  is  extremely  unhkely  that  the  fluids  of  the  body 
are  ever,  in  gouty  subjects,  saturated  with  so  soluble  a 


196  GOUT:    INVESTIGATIONS.  [Partiii. 

compound  as  the  sodium  quadriurate  ;  therefore,  it  is 
but  fair  to  infer  that,  with  smaller  proportions  of  the 
quadriurate  in  solution,  the  inhibitory  effects  of  the 
mineral  constituents  of  vegetables  would  extend  over  much 
longer  periods  than  actually  occurred  in  the  carrying  out 
of  these  experiments. 

Results  of  the  experimental  inquiry. — The  net  re- 
sults of  all  the  experiments  described  indicate  that  the 
mineral  constituents  of  most  vegetables  increase  the  solu- 
bility of  sodium  biurate,  and  also,  in  several  cases,  delay 
for  considerable  periods  the  conversion  of  the  sodium 
quadriurate  into  the  biurate.  On  the  other  hand,  the 
mineral  constituents  of  meat  diminish  the  solubility  of 
sodium  biurate,  and  exercise  but  little  effect  in  delaying 
the  conversion  of  the  quadriurate  into  the  biurate. 

I  wish  it  to  be  clearly  understood  that  I  do  not  attri- 
bute the  different  effects  of  animal  and  vegetable  diets 
on  gouty  subjects  to  the  saline  constituents  alone.  I 
think,  however,  that  the  results  of  these  experiments 
clearly  show  that  it  is  to  the  different  mineral  constituents 
of  animal  and  vegetable  foods,  and  to  the  different  physical 
effects  they  exercise  on  the  quadriurate  and  biurate,  that 
we  must  look  for  a  partial  explanation  of  the  known  facts 
that  an  excessive  diet  of  the  one  tends  to  produce  gout 
and  of  the  other  tends  to  retard  it. 

A  reference  to  some  of  the  tables  previously  given 
will  show  that  certain  vegetables  stand  out  prominently 
with  regard  to  the  effect  exercised  by  their  mineral  con- 
stituents both  in  retarding  the  conversion  of  the  sodium 
quadriurate  into  the  biurate,  and  in  increasing  the  solu- 
bility of  the  latter.  These  vegetables  are  spinach,  Brussels 
sprouts,  French  beans,  winter  cabbage,  Savoy  cabbage, 
turnip  tops,  turnips,  and  celery.  These  are  the  vegetables 
which  I  consider  are  likely  to  prove  most  beneficial  to 
gouty  subjects.  Of  these,  in  so  far  as  the  effects  produced 
by  their  mineral  constituents  are  concerned,  spinach  occupies 


chap.x]  vegetables    and    gout.  197 

the  lirst  place,  both  as  regards  inhibiting  the  decomposition 
of  the  quadriurate  and  increasing  the  solubihty  of  the  biurate. 
Spinach  has  the  further  advantage  of  being  extremely 
rich  in  mineral  constituents,  since  it  contains  16.27  P^^ 
cent,  of  mineral  matter  as  compared  with  8.50,  which 
is  the  average  percentage  of  the  mineral  constituents  of 
all  the  vegetables  experimented  with.  It  may  be  urged 
that  a  drawback  to  the  employment  of  spinach  is  that  it 
cannot  be  obtained  fresh  throughout  the  year.  Very 
excellent  spinach  is,  however,  now  obtainable  in  the  desic- 
cated and  compressed  state,  and  when  cooked  makes  a 
dish  which  is  practically  indistinguishable  from  the  fresh 
vegetable. 

General  conclusions  drawn  from  the  investigfations. 

1.  The     solubility   of     sodium    biurate    is   markedly 

increased  by  the  presence  of  the  mineral  con- 
stituents of  most  vegetables. 

2.  The    mineral    constituents    of    certain    vegetables 

delay  the  conversion  of  sodium  quadriurate  into 
the  biurate. 

3.  The  vegetables  most   useful  to  gouty  subjects  are 

spinach,  Brussels  sprouts,  French  beans,  winter 
cabbage,  Savoy  cabbage,  turnip  tops,  turnips, 
and  celery. 


CHAPTER    XI. 
SOLUTION   OF   GOUTY   DEPOSITS. 

Reasons  for  believing  that  the  removal  of  gouty  deposits  by 
alkalies  is  erroneous — Experimental  investigation  of  the  value 
of  the  various  alkalies,  piperazine,  and  lysidine  as  solvents 
of  gouty  deposits — Experimental  investigation  of  the  value 
of  salicylates  as  solvents  of  gouty  deposits. 

For  a  considerable  period  of  time  two  methods  of  treat- 
ment which  have  for  their  professed  object  the  ehmination 
of  uric  acid  from  the  system  have  been  more  or  less  em- 
ployed by  medical  men.  They  are  the  treatment  of  gout 
by  means  of  alkalies,  and  by  means  of  salicylates.  These 
two  methods  of  treatment  I  consider  owe  their  popularity 
to  the  entirely  erroneous  supposition  that  uric  acid  is 
present  as  such  in  the  fluids  and  deposits  of  gouty  patients, 
whereas  the  uric  acid  is  always  present  as  sodium  quadri- 
urate  or  biurate,  and  the  chemical  and  physical  behaviour 
of  these  substances  is  entirely  different  from  that  of  uric 
acid. 

The  plea  for  the  treatment  of  gout  by  means  of  alkalies 
is  mainly  based  on  the  following  assumptions  : — (i)  That 
uric  acid  is  present  in  the  blood  and  tissues,  and  is  rendered 
soluble  by  the  administration  of  alkalies  ;  (2)  that  the 
biurate  deposited  in  joints  is  rendered  soluble  by  means 
of  alkalies  ;  and  (3)  that  there  is  a  general  acidity  of  the 
system  which  is  neutralised  and  removed  by  alkalies.  It 
will  be  seen  that  these  assumptions  do  not  stand  the  test 
of  experimental  inquiry.  With  regard  to  the  first  assump- 
tion, it  is  now  well  known  that  in  gouty  subjects  uric  acid 
is  never  present  as  such  in  the  blood  and  tissues,  but  is 
always  combined  with  sodium  as  the  quadriurate  or  biurate, 


Chap.  XL]  ALKALIES    AND    GOUT. 


199 


and  possibly  in  some  organic  combination  as  well.  The 
only  way  in  which  alkalies  could  beneficially  affect  the 
quadriurate  would  be  to  delay  its  conversion  into  the 
biurate.  In  order  to  test  this  point,  I  conducted  a  series 
of  experiments  so  as  to  ascertain  the  effect  of  artificial 
blood  serum,  to  which  different  alkalies  had  been  added, 
on  the  decomposition  of  sodium  quadriurate.  In  all  the 
experiments  the  artificial  blood  serum  employed  was  Sir 
William  Roberts's  standard  solution.  This  was  employed 
instead  of  blood  serum  in  order  to  obviate  the  objections 
that  have  been  raised  to  the  use  of  blood  serum  in  such 
experiments,  viz.  the  tendency  to  variation  in  its  alkalinity. 
Moreover,  as  shown  by  Sir  William  Roberts,  this  standard 
solution  reacts  with  uric  acid  and  with  the  quadriurates 
and  biurates  in  the  same  manner  as  blood  serum  itself. 

Objects  of  conducting-  the  experiments  with  sodium 
quadriurate. — These  experiments  were  undertaken  in 
order  to  ascertain  whether  any  of  the  drugs  ordinarily 
employed  in  the  alkaline  treatment  of  gout  possess  any 
power,  when  introduced  into  the  circulation,  of  restraining 
the  precipitation  of  sodium  biurate  from  the  quadriurate 
contained  in  the  blood.  Such  experiments  would  show 
whether  any  such  drugs  would  be  of  use  in  lessening  the 
formation  of  gouty  deposits. 

When  sodium  quadriurate  is  mixed  with  water  it  is 
decomposed  into  a  uric  acid  moiety  and  a  sodium  biurate 
moiety,  the  uric  acid  appearing,  immediately  it  is  set  free, 
in  the  form  of  ovoid  or  spindle-shaped  crystals.  These 
crystals  appear  in  a  very  short  time  after  the  contact  of 
the  quadriurate  with  water — generally  in  from  one  to  five 
minutes — whilst  the  sodium  biurate  passes  into  the  gela- 
tinous form,  which,  if  sufficient  water  be  present,  is  dis- 
solved. If,  instead  of  water,  an  alkaline  medium  be  em- 
ployed to  decompose  the  quadriurate,  such  as  blood  serum 
or  artificial  blood  serum,  at  the  temperature  of  the  human 
body,  then  as  long  as  free  alkaline  carbonate  is  present 


2o6  'GOUT:    INVESl'lGATIONS.  [PARxiit. 

the  uric  acid  moiety  of  the  quadriurate,  instead  of  crystal- 
hsing  out  as  uric  acid,  unites  with  tlie  sodium  carbonate 
to  form  sodium  biurate,  which  first  assumes  the  amor- 
phous form.  After  a  time  this  amorphous  biurate  becomes 
gradually  converted  into  the  needles  of  the  crystalline 
biurate.  The  time,  therefore,  that  elapses  between  the 
saturation  of  the  blood  serum  with  sodium  quadriurate, 
and  the  first  appearance  of  needle-shaped  crystals  of  sodium 
biurate,  represents  the  inhibitory  influence  of  the  medium 
on  the  crystalline  precipitation  of  sodium  biurate.  The 
next  paragraph  describes  how  the  experiments  to  ascertain 
the  effect  of  drugs  employed  in  the  alkaline  treatment  of 
gout  were  conducted. 

Method  of  conducting"  the  experiments  with  sodium 
quadriurate, — Ten  milligrammes  of  sodium  quadriurate 
were  well  rubbed  with  ten  drops  of  a  o.i  per  cent,  solution 
of  the  drug  in  artificial  blood  serum,  and  the  mixture  was 
then  placed  in  a  small  corked  tube  and  kept  at  ioo°  F. 
Every  half-hour  a  small  quantity  of  the  mixture  was  re- 
moved and  examined  under  a  high  power  of  the  microscope, 
and  the  time  at  which  crystals  of  the  sodium  biurate  first 
appeared  was  noted.  A  similar  experiment,  for  purposes 
of  comparison,  was  made  with  the  quadriurate  and  artificial 
blood  serum  alone.  I  experimented  separately  in  this 
way  with  potassium  bicarbonate,  potassium  citrate,  lithium 
carbonate,  lithium  citrate,  sodium  bicarbonate,  sodium 
phosphate,  piperazine,  and  lysidine.  The  results  are  set 
out  in  Table  XLVI.  They  show  that  none  of  the  drugs 
mentioned  in  the  table  exercises  the  slightest  effect  in 
delaying  the  conversion  of  the  quadriurate  into  the  biurate, 
even  when  present  in  far  larger  proportions  than  could 
possibly  be  introduced  into  the  blood  by  the  medicinal 
administration  of  the  drugs.  Therefore  it  appears  that 
the  treatment  of  gout  by  alkalies  and  salts  of  the  alkalies 
does  not  delay  the  conversion  of  the  quadriurate  into  the 
biurate. 


Chap.  Xl.] 


Alkalies  and  gout. 

TABLE    XLVI. 


201 


Showing  the  influence  exerted  on  the  decomposition  of  sodium  quadri- 
urate  by  artificial  blood  serum  alone,  and  by  artificial  blood  serum 
containing  o .  i  per  cent,  of  various  drugs  in  solution. 


Solvent. 


Sodium  biurate  crys- 
tals appeared  after 
the  lapse  of — 


Artificial  blood 


serum. 

„     containing  o.  I  per  cent,  of 

potassium   bicarbonate 
,,     containing  o.  i  per  cent,  of 

potassium  citrate   . 
,,     containing  o.  i  per  cent,  of 

lithium  carbonate 
„     containing o.  I  per  cent,  of 

lithium  citrate 
,,     containing  o.  i  per  cent,  of 

sodium  bicarbonate     . 
,,     containing  o.  i  per  cent,  of 

sodium  phosphate 
,,     containing  o .  i  per  cent,  of 

piperazine  .... 
,,     containing  o .  i  per  cent,  of 

lysidine       .... 


2  hours 


Does  the  treatment  of  grout  by  alkalies  increase 
the  solubility  of  sodium  biurate  ? — With  regard  to 
the  second  assumption,  that  the  administration  of  alkalies 
increases  the  solubility  of  the  biurate  deposited  in  the 
joints  and  tissues,  Sir  William  Roberts  *  has  shown  that 
sodium  bicarbonate  and  sodium  phosphate  diminish  the 
solubility  of  sodium  biurate,  while  potassium  bicarbonate 
exercises  no  influence  whatever  on  its  solubility.  That 
the  administration  of  alkalies  might  increase  the  solubility 
of  the  biurate  appeared  at  one  time  to  be  probable  from 
the  results  of  some  experiments  performed  by  Sir  Alfred 
Garrod.  He  immersed  small  pieces  of  cartilage  infiltrated 
with  sodium  biurate  for  forty-eight  hours  in  aqueous 
solutions  of  the  carbonates  of  lithium,  potassium,  and 
sodium  respectively.     At  the  end  of  that  time  he  found 


Croonian  Lectures,  1892. 


202  GOUT:    INVESTIGATIONS.  [partiii. 

that  the  cartilage  immersed  in  the  lithium  solution  was 
restored  to  its  natural  condition  ;  that  in  the  potassium 
solution  was  much  acted  upon,  while  that  in  the  sodium 
solution  appeared  to  be  unaltered.  These  results  are 
somewhat  in  opposition  to  those  of  Sir  William  Roberts, 
and  as  neither  the  experiments  of  Sir  Alfred  Garrod  nor 
those  of  Sir  William  Roberts  represent  the  conditions  under 
which  alkalies,  when  introduced  into  the  circulation,  would 
act  on  sodium  biurate,  I  thought  it  desirable  to  re-investigate 
the  subject,  as  far  as  possible  under  such  conditions. 

Investigration  of  the  effects  of  various  alkaline  drug's 
on  the  solubility  of  sodium  biurate. — These  experiments 
were  undertaken  in  order  to  compare  the  solubility  at 
100°  F.  of  sodium  biurate  in  artificial  blood  serum,  and 
in  artificial  blood  serum  containing  different  proportions 
of  the  various  drugs.  The  experiments  were  carried  out  in 
a  similar  manner  to  those  previously  described.  I  experi- 
mented separately  with  the  following  drugs,  viz.  potassium 
bicarbonate,  potassium  citrate,  lithium  carbonate,  lithium 
citrate,  sodium  bicarbonate,  sodium  phosphate,  piperazine, 
and  lysidine.  Much  greater  proportions  of  the  drugs  were 
employed  than  could  possibly  be  introduced  into  the  blood 
by  medicinal  administration.  The  results  are  shown  in  the 
following  tables  : — 

TABLE    XLVII. 

Showing  the  solubility  at  ioo°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportiovis  of  potassium  bicarbonate. 


Solvent. 


Artificial  blood  serum 

Artificial   blood    serum   containing   o.oi    per 

cent,  of  potassium  bicarbonate 
Artificial   blood   serum   containing   o.io   per 

cent,  of  potassium  bicarbonate 
Artificial   blood   serum   containing   0.20   per 

cent,  of  potassium  bicarbonate 


Sodium  biurate 
dissolved. 


o.  II  per  1,000 
0.10  ,, 

0.10 
o.  II 


ALKALIES    AND    GOUT. 


203 


HAP.  XI.] 

These  results  show  that  potassium  bicarbonate  would 
not  in  the  slightest  degree  increase  the  solvent  power  of 
the  blood  for  gouty  deposits. 

TABLE    XLVIII. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  potassium  citrate. 


Solvent. 


Artificial  blood  serum 

Artificial    blood   serum   containing   o.oi    per 

cent,  of  potassium  citrate 

Artificial    blood    serum    containing   o.io    per 

cent,  of  potassium  citrate 

Artificial    blood   serum    containing   0.20    per 

cent,  of  potassium  citrate 


Sodium  biurate 
dissolved. 


o .  1 1  per  1 ,000 
0.10         ,, 
0.10 
o.  I  I 


These  results  show  that  potassium  citrate  would  not 
in  the  slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits. 

TABLE    XLIX. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  lithium  carbonate. 


Solvent. 

Sodium  biurate 
dissolved. 

Artificial  blood  serum - 

0. 1 1  per  1,000 

Artificial  blood  serum  containing  0.005 

per 

cent,  of  lithium  carbonate    . 

0. 1 1 

Artificial    blood   serum   containing   o.oi 

per 

cent,  of  lithium  carbonate    . 

0.  II 

Artificial   blood   serum    containing   0. 10 

per 

cent,  of  lithium  carbonate    . 

0.15 

These  results  show  that  lithium  carbonate  would  not 
in  the  slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits,  even  when  present  in  far  larger 
proportions  than  could  be  introduced  into  the  blood  by 
medicinal  administration.      Lithium  salts  are  usually  given 


204 


GOUT:    INVESTIGATIONS. 


[Part  III. 


in  doses  of  one  to  five  grains  three  times  a  day,  whereas  to 
get  o.oi  per  cent,  of  a  hthium  salt  into  the  blood  it  would 
be  necessary  to  introduce  lo  grains  of  the  salt  at  once 
into  the  circulation  of  an  adult  man  of  average  weight. 

TABLE    L. 

Showing  the  solubility  at  ioo°  -F.  of  sodium  biurate  in  artificial  hlood 
serum  alone,  and  in  artificial  hlood  serum  containing  different 
proportions  of  lithium  citrate. 


Solvent. 

Sodium  biurate 
dissolved. 

Artificial  blood  serum 

0 . 1 1   per  1 ,000 

O.II 

Artificial  blood  serum  containing  0.005 
cent,  of  lithium  citrate    .... 

per 

Artificial   blood    serum   containing   o.oi 
cent,  of  lithium  citrate    .... 

per 

O.II 

Artificial   blood   serum   containing   o.io 
cent,  of  lithium  citrate   .... 

per 

O.II 

These  results  show  that  lithium  citrate  would  not  in 
the  slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits. 

TABLE    LI. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  sodium  bicarbonate. 


Solvent. 


Sodium  biurate 
dissolved. 


Artificial  blood  serum 

Artificial   blood   serum    containing   o.oi    per 

cent,  of  sodium  bicarbonate  .... 
Artificial   blood    serum   containing   o.io    per 

cent,  of  sodium  bicarbonate  .... 
Artificial    blood    serum    containing   o .  20    per 

cent,  of  sodium  bicarbonate       .... 


O.II  per  1,000 
O.IO  ,, 

o .  09 
0.08 


These  results  show  that  sodium  bicarbonate  would 
slightly  decrease  the  solvent  power  of  the  blood  for  gouty 
deposits. 


Chap.  XI.]  PIPERAZINE    AND    GOUT. 

TABLE    LII. 


205 


Showing  the  solubility  at  100°  F.-of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  sodium  phosphate. 


Solvent. 


Sodium  biurate 
dissolved. 


Artificial  blood  serum 

Artificial    blood    serum   containing   o.oi    per 

cent,  of  sodium  phosphate 

Artificial    blood    serum   containing   o.io    per 

cent,  of  sodium  phosphate 

Artificial    blood    serum   containing   o .  20    per 

cent,  of  sodium  phosphate 


o .  1 1  per  1 ,000 
o.  I  I 
O.  II 
O.  II 


These  results  show  that  sodium  phosphate  would  not 
in  the  slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits. 

TABLE    LIII. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  piperazine. 


Solvent. 


Sodium  biurate 
dissolved. 


Artificial  blood  serum 

Artificial   blood    serum   containing   o.oi    per 

cent,  of  piperazine 

Artificial    blood    serum   containing   o.io   per 

cent,  of  piperazine 

Artificial   blood   serum   containing   o .  20   per 

cent,  of  piperazine 


o .  II  per  1 ,000 
0.09 

O.II 

0.13 


These  results  show  that  piperazine  would  not  in  the 
slightest  degree  increase  the  solvent  power  of  the  blood  for 
gouty  deposits,  even  when  present  in  far  larger  proportions 
than  could  be  introduced  into  the  blood  by  medicinal 
administration,  Piperazine  is  usually  given  in  doses  of 
five  grains  three  times  a  day,  whereas  to  get  o.io  per  cent, 
of    piperazine   into   the   blood    it  would    be    necessary   to 


2o6  GOUT:    INVESTIGATIONS.  [Partiii. 

introduce    lOO  grains  of   the  drug  at  once  into  the  circula- 
tion of  an  adult  man  of  average  weight. 

TABLE    LIV. 

Showing  the  solubility  at  ioo°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  lysidine. 


Solvent. 


Sodium  biurate 
dissolved. 


Artificial  blood  serum 

Artificial   blood   serum   containing   o.oi    per 

cent,  of  lysidine 

Artificial   blood    serum    containing   o.io    per 

cent,  of  lysidine 

Artificial   blood    serum   containing   0.20    per 

cent,  of  lysidine 


o .  1 1  per  1 ,000 

o .  09 

0.10 

0.10 


These  results  show  that  lysidine  would  not  in  the  slight- 
est degree  increase  the  solvent  power  of  the  blood  for  gouty 
deposits,  even  when  present  in  far  larger  proportions  than 
could  be  introduced  into  the  blood  by  medicinal  admin- 
istration. Lysidine  is  given  in  doses  of  from  30  to  120 
grains  three  times  a  day,  whereas  to  get  0.20  per  cent, 
of  lysidine  into  the  blood  it  would  be  necessary  to  intro- 
duce 200  grains  of  the  drug  at  once  into  the  circulation 
of  an  adult  man  of  average  weight. 

Further  experiments  as  to  the  influence  of  potas- 
sium and  lithium  salts  on  the  solvency  of  grouty 
deposits. — As  it  appeared  to  me  that  the  experiments 
of  Sir  Alfred  Garrod,  previously  referred  to,  as  to  the 
solvent  effect  of  potassium  bicarbonate  and  lithium  car- 
bonate on  gouty  deposits,  were  scarcely  comparable  with 
what  occurs  when  those  drugs  are  acting  via  the  blood 
and  other  fluids  of  the  body,  I  thought  it  desirable  to 
repeat  the  experiments  under  different  conditions.  I 
therefore  investigated  the  solvent  action  on  gouty  deposits 
of  artificial  blood  serum  impregnated  with  quantities  of 
potassium  bicarbonate  and  lithium  carbonate  respectively  ; 


Chap.  XI.]  ALKALIES    AND    GOUT.  207 

the  quantities  of  the  drugs  used  were  as  nearly  as  possible 
equal  to  those  which  would  be  present  in  the  fluids  of  the 
human  body  when  full  doses  are  being  administered.  The 
artificial  blood  serum  impregnated  with  potassium  bicar- 
bonate contained  o.oi  per  cent,  of  that  drug.  The  artificial 
blood  serum  impregnated  with  lithium  carbonate  contained 
0.0015  P^r  cent,  of  that  drug.  The  experiments  were 
carried  out  in  the  following  manner. 

Method  of  ascertaining-  the  solvent  effects  of  potas- 
sium bicarbonate  and  lithium  carbonate  on  g-outy 
deposits. — A  piece  of  cartilage  well  and  uniformly  infil- 
trated with  sodium  biurate,  which  had  been  removed  from 
a  gouty  joint  at  a  post-mortem  examination,  was  divided 
into  three  equal  pieces.  One  piece  was  suspended  in  a 
bottle  containing  100  c.c.  of  artificial  blood  serum,  the 
second  piece  in  a  bottle  containing  100  c.c.  of  artificial 
blood  serum  impregnated  with  potassium  bicarbonate, 
and  the  third  piece  in  a  bottle  containing  100  c.c.  of  artificial 
blood  serum  impregnated  with  lithium  carbonate.  The 
bottles  with  their  contents  were  kept  throughout  the  ex- 
periments at  the  blood  heat,  and  every  twenty-four  hours 
fresh  supplies  of  fluid  were  introduced,  so  that  the 
first  piece  of  cartilage  was  constantly  bathed  in  artificial 
blood  serum  at  the  blood  heat,  the  second  piece  in 
artificial  blood  serum  impregnated  with  potassium 
bicarbonate,  and  the  third  piece  in  artificial  blood 
serum  impregnated  with  lithium  carbonate.  By  this 
method  of  procedure  it  was  considered,  as  regards  any 
solvent  effect  that  the  drugs  might  exert  on  the  gouty 
deposit,  that  the  results  would  be  fairly  comparable  with 
what  occurs  when  potassium  or  lithium  salts  are  medicin- 
ally administered.  The  pieces  of  cartilage  were  removed 
every  twenty-four  hours  and  examined  by  means  of  a 
lens,  and  the  experiments  were  continued  until  all  the 
sodium  biurate  was  dissolved  out  of  the  cartilage.  The 
solution  of  the  sodium  biurate  from  the  cartilage  proceeded 


2o8  GOUT:    INVESTIGATIONS.  [Partiii. 

at  the  same  pace  in  the  three  pieces,  and  was  in  no  way 
accelerated  by  the  presence  of  the  potassium  bicarbonate 
or  the  Hthium  carbonate.  The  sodium  biurate  was  com- 
pletely dissolved  from  the  three  pieces  of  cartilage  on 
the  fifteenth  day. 

These  experiments  indicate  that  the  quantities  of 
potassium  bicarbonate  and  lithium  carbonate  that  could, 
by  ordinary  dosage,  be  introduced  into  the  fluids  of  the 
body  can  exercise  no  influence  on  the  solvency  of  gouty 
deposits,  and  the  results  obtained  support  the  view  of 
Sir  William  Roberts  that  potassium  bicarbonate  and 
lithium  carbonate  exercise  no  influence  on  the  solubility 
of  sodium  biurate.  The  net  result  of  all  these  experiments 
is  that  the  treatment  of  gout  by  alkalies  or  by  piperazine 
or  lysidine  does  not  increase  the  solubility  of  the  biurate 
deposited  in  the  joints  and  tissues.  Levison  *  holds  very 
similar  opinions  with  regard  to  the  alkaline  treatment  of 
gout.  He  considers  that  the  administration  of  the  ordinary 
alkalies,  of  lithium  salts,  or  of  piperazine  with  the  object 
of  either  dissolving  sodium  biurate  or  of  preventing  its 
deposition  is  decidedly  useless.  He  also  found  that  the 
administration  of  piperazine  exerts  no  influence  upon 
the  amount  of  uric  acid  excreted. 

J.  Fawcett,t  as  the  result  of  his  investigations  on  the 
treatment  of  gout  by  piperazine,  arrives  at  an  unfavour- 
able conclusion  as  to  its  efficacy  in  gout.  He  found  that 
in  acute  cases  it  did  not  relieve  the  pain,  nor  was  there 
any  constant  increase  in  the  excretion  of  uric  acid  under 
its  use.  Mordhorst  J  also  considers  that  piperazine  and 
lysidine  are  useless  in  the  treatment  of  gout. 

A  g-enepal  acidity  of  the  system  not  associated 
with  gout. — The  third  assumption,  that  in  connection 
with  gout  there  is  a  general  acidity  of  the  system  which 

*  "The  Uric  Acid  Diathesis,"   1894. 

t  Guy's  Hosp.  Reports,  1895. 

J  Therap.  Monats.,  x.,  1896.  ... 


CAP.  XI.]  ALKALINITY    OF    BLOOD.  209 

causes  a  diminished  alkalinity  of  the  blood,  is  opposed 
to  the  results  of  recent  investigations  on  the  subject.  The 
experiments  of  Klemperer  and  my  own  experiments  show 
that  the  alkalinity  of  the  blood  of  gout  is  not  diminished, 
and  that  variations  in  the  alkalinity  of  the  blood  may 
frequently  be  met  with  in  healthy  individuals.  More- 
over, the  experiments  previously  described  demon- 
strate that  a  diminution  in  the  alkalinity  of  blood  serum 
containing  uric  acid  in  solution  does  not  facilitate  the 
deposition  of  sodium  biurate  from  it,  nor  does  a  diminution 
in  the  alkalinity  of  blood  serum  diminish  its  solvent  power 
for  sodium  biurate.  It  appears  therefore  that  there  is  no 
ground  whatever  for  the  assumption  that  the  treatment 
of  gout  by  alkalies  tends  to  neutralise  a  so-called  general 
acidity  of  the  system,  and  so  renders  the  blood  a  better 
solvent  of  gouty  deposits. 

No  relationship  between  the  acidity  of  the  urine 
and  the  alkalinity  of  the  blood. — The  idea  that  a  general 
acidity  of  the  system  is  associated  with  gout  has,  in  my 
opinion,  arisen  from  observations  of  the  fact  that  the 
urine  of  gouty  patients  is  acid.  These  observations  are 
generally  made  on  small  samples  of  the  urine,  although 
when  the  total  acidity  of  the  urine  for  the  twenty-four 
hours  is  determined,  it  is  frequently  found  to  be  below 
that  of  the  normal  acid  output  in  the  urine  for  that  period 
of  time.  It  is  certain  that  the  erroneous  assumption  has 
been  made  by  some  writers  that  variations  in  the  acidity 
of  the  urine  can  be  taken  as  a  gauge  of  corresponding 
variations  in  the  alkalinity  of  the  blood,  and  that  therefore 
a  fall  of  acidity  in  the  urine  means  an  increased  alkalinity 
of  the  blood,  and  vice  versa.  That  this  assumption  is  quite 
wrong  is  shown  by  reference  to  the  next  table  (Table  LV.), 
in  which  are  arranged  side  by  side  the  determinations 
that  I  made  on  the  same  days  of  the  alkalinity  of  the 
blood  and  of  the  total  acidity  of  the  urine  for  each  twenty- 
four  hours   of   an   adult   patient   suffering   from   subacute 


210 


GOUT:    INVESTIGATIONS. 


[Part  III. 


gout.    The  total  acidity  of  the  urine  was  determined  by 

collecting  the  whole  of  the  urine  for  the  twenty-four  hours, 

and  then  titrating  a  portion  of  the  urine  by  the  process 

described    by    Lepinois.*     The    estimations    were    made 

mostly  on  alternate  days  throughout  the  duration  of  the 

attack. 

TABLE    LV. 

Shoiving  the  absence  of  any  constant  relationship  between  the  alkalinity 
of  the  blood  and  the  acidity  of  the  urine  of  a  patient  during  an 
attack  of  subacute  govit. 


Alkalinity  represented  as 

Acidity   of    total    urine     for 

Dates   of 

percentage    of    anhy- 

the   24  hours,    reckoned  as 

determinations. 

drous  sodium  carbon- 
ate    present     in     the 
blood. 

grammes     of     hydrochloric 
acid. 

Feb.  4th. 

0.  167 

1.392 

,    6th. 

0.  167 

0 

953 

,    8th. 

0.  167 

096 

,  loth. 

0.  156 

374 

,  1 2th. 

0. 167 

583 

,  15th. 

0.158 

529 

1              , 

,  17th. 

0.158 

629 

,  19th. 

0.  167 

581 

, 22nd. 

0.  180 

602 

,  24th. 

0.173 

Alkaline 

I 

,  26th. 

0.  i6r 

Alkaline 

,  28th. 

0.179 

0.608 

Mar.  2nd. 

0. 167 

0.622 

This  table  shows  that  no  constant  relationship  existed 
in  this  case  of  gout  between  the  alkalinity  of  the  blood 
and  the  acidity  of  the  urine,  and  moreover  that  on  those 
days  when,  owing  to  treatment  with  citrate  of  potassium, 
which  was  administered  from  February  19th  to  28th,  the 
urine  remained  alkaline,  there  was  no  corresponding  rise 
in  the  alkalinity  of  the  blood. 

These  determinations  of  the  alkalinity  of  the  blood 
and  the  acidity  of  the  urine  of  this  case  of  subacute  gout 
are  shown  in  curves  in  the  following  diagram,  a  glance  at 


*  Jonrn.  Pharm.,  1896  (6),  iii.,    8-16. 


Chap.  XI.] 


SALICYLATES    AND    GOUT. 


211 


which  at  once  demonstrates  that  no  constant  relationship 
existed  between  the  alkahnity  of  the  blood  and  the 
acidity  of  the  urine. 

Reasons  for  believingr  the  treatment  of  g'out  by  sali- 
cylates to  be  erroneous.  —  Just  as  the  treatment  of 
gout  by  means  of  alkalies  is  based  on  the  entirely  erroneous 
supposition  that  uric  acid  is  present  as  such  in  the  fluids 
and  deposits  of  gouty  patients,   so   the   main  reason   for 


A 

A 

\, 

/ 

\ 

y 

y 

^-«> 

^ 

/ 

^ 

\ 

/ 

"'v 

y 

B 

/ 

""*■". 

''' 

~~' 

'"" 

I 

• 

\ 

'" 

\ 
1 

1 
\ 

/ 

— 

\ 

\ 

Mi 

iuL 

\'cili 

^ 

of 

Ur 

tne 

\ 

/ 

~^" 

PiLM 

■•""■ 

^^ 

JIL 

*^ 

^^ 

• 

Diagram  showing  the  absence  of  any  constant  relationship  between 
the  alkalinity  of  the  blood  and  the  acidity  of  the  urine  of  a 
patient  during  an  attack  of  subacute  gout. 

A,  Alkalinity  of  blood.         B,  Acidity  of  urine. 

giving  a  salicylate  in  gout  is  based  on  the  assumption 
that  it  unites  with  uric  acid  throughout  the  system,  and 
so  effects  its  removal  from  the  system  and  its  elimination 
in  the  urine.  That  sodium  salicylate  does  cause  an  in- 
creased elimination  of  uric  acid  in  the  urine,  at  all  events 
in  the  early  stages  of  its  administration,  is  undoubted. 
This  is  shown  by  the  following  daily  determinations  that 
I  made  of  the  total  uric  acid  excretion  of  a  healthy 
man   before,    during,    and    after    treatment    with    sodium 


212  GOUT :  INVESTIGATIONS.  [partiii. 

salicylate.     The  diet  was  of   the  same  nature  throughout 
the  experiment. 

TABLE    LVI. 

Showing  the  daily  excretion  on  successive  days  of  uric  acid  by  a 
healthy  man  before,  during,  and  after  treatment  with  sodium 
salicylate. 


Daily  excretion  of  uric 
acid  in  grammes. 


/O.S47 

Before  taking  salicylate '0.589 

(  0.731 

Average 0.622 

[-0.852 
Fifteen  grains  of  sodium  salicylate  taken   .  Jo.  942 

three  times  a  day ]  0.826 

t 0.784 

Average 0.851 


r 0.340 
jo. 581 

Salicylate  left  off J^  0.543 

0.677 
0.686 

Average 0.565 


That  this  increased  elimination  of  uric  acid  is  due, 
however,  to  the  removal  of  ready-formed  uric  acid  stored 
in  the  system  is,  in  my  opinion,  incorrect.  In  the  first 
place  it  must  be  remembered  that  any  uric  acid  deposited 
in  any  of  the  organs  or  tissues  of  gouty  subjects  is  deposited 
in  the  form  of  sodium  biurate,  and  the  results  of  the  follow- 
ing experiments  show  that  artificial  blood  serum  contain- 
ing sodium  salicylate,  in  much  greater  proportions  than 
could    be    introduced    into  the  blood   by  the    medicinal 


Chap.  XI]  SALICYLATES    AND    GOUT.  213 

administration  of  the  drug,  has  not  the  shghtest  increased 
solvent  effect  on  the  biurate. 

TABLE    LVII. 

Showing  the  solubility  at  100°  F.  of  sodium  biurate  in  artificial  blood 
serum  alone,  and  in  artificial  blood  serum  containing  different 
proportions  of  sodium  salicylate. 


Solvent. 

Sodium  biurate 
dissolved. 

Artificial  blood  serum 

0. 1 1   per  1,000 

Artificial  blood  serum  containing  0.003 

per 

cent,  of  sodium  salicylate     . 

O.II 

Artificial  blood  serum  containing  0.006 

per 

cent,  of  sodium  salicylate 

O.II          ,, 

Artificial   blood   serum   containing   o.oi 

per 

cent,  of  sodium  salicylate 

O.II            „ 

Artificial   blood    serum    containing   o.io 

per 

cent,  of  sodium  salicylate 

O.II 

These  results  show  that  sodium  salicylate  would  not 
in  the  slightest  degree  increase  the  solvent  power  of  the 
blood  for  gouty  deposits,  even  when  present  in  far  larger 
proportions  than  could  be  introduced  into  the  blood  by 
medicinal  administration.  Sodium  salicylate  is  usually 
given,  in  the  treatment  of  gout,  in  doses  of  fifteen  to  twenty 
grains  three  times  a  day,  whereas  to  get  o.i  per  cent,  of 
sodium  salicylate  into  the  blood  it  would  be  necessary 
to  introduce  100  grains  of  the  drug  at  once  into  the  circu- 
lation of  an  adult  man  of  average  weight.  J.  Fawcett,* 
who  likewise  finds  that  sodium  salicylate  produces  an 
increased  uric  acid  excretion,  considers  it  improbable 
that  the  increase  can  be  explained  by  a  mere  clearing  out 
of  retained  uric  acid. 

I  also  find  that  artificial  blood  serum  containing  sodium 
salicylate  in  far  larger  proportions  than  could  be  intro- 
duced into  the  blood  by  medicinal  administration  has  no 
effect  whatever  in  delaying  the  conversion  of  sodium  quadri- 
urate  into  the  biurate,  as  is  shown  in  the  following  table  : — 

*  Guys  Hosp.  Reports,  1895. 


214  GOUT:    INVESTIGATIONS.  [PariIII. 

TABLE    LVIII. 

Showing  the  influence  exerted  on  the  decomposition  of  sodium  quadri- 
urate  by  artificial  blood  serum,  and  by  artificial  blood  serum 
containing  o.i   per  cent,  of  sodium  salicylate  in  solution. 


Solvent. 

Sodium  biurate  crys- 
tals appeared  after 
the  lapse  of — 

Artificial  blood  serum 

Artificial    blood    serum    containing    o .  i    per   . 
cent,  of  sodium  salicylate 

2  hours. 
2  hours. 

It  therefore  appears  from  the  results  of  the  experiments 
given  in  Tables  LVII.  and  LVIII.  that  sodium  salicylate 
has  no  direct  action  either  in  delaying  the  decomposition 
of  sodium  quadriurate  or  in  effecting  a  solvent  action  on 
deposits  of  sodium  biurate.  The  erroneous  supposition  as 
to  salicylates  possessing  a  solvent  power  on  gouty  deposits 
probably  arose  from  the  faulty  deduction  that  increased 
elimination  of  uric  acid  in  the  urine  after  the  administration 
of  a  salicylate  was  necessarily  due  to  the  solvent  effect 
of  the  salicylate  on  uratic  deposits.  The  correct  explana- 
tion of  this  increased  elimination  of  uric  acid  is,  I  believe, 
to  be  found  in  the  known  fact  that  salicylic  acid  unites 
readily  with  glycocine  to  form  salicyluric  acid,  and  that 
it  thus  brings  an  increased  amount  of  glycocine  to  the 
kidneys,  where  by  the  combination  of  that  body  with 
urea  an  increased  amount  of  uric  acid  may  be  formed. 

General  conclusions  drawn  from  the  investigrations. 

1.  The   administration    of    the   ordinary   alkalies,    of 

lithium  salts,  of  piperazine,  and  of  lysidine,  with 
the  object  of  removing  gouty  deposits,  appears 
to  be  useless. 

2.  No    general   acidity   of    the   system   is    associated 

with  gout. 

3.  No  relationship  exists  between  the  acidity  of  the 

urine  and  the  alkalinity  of  the  blood. 

4.  The   administration  of  salicylates  with  the  object 

of  removing  gouty  deposits  appears  to  be  useless. 


PART  IV. 

THE  TREATMENT  OF  GOUT  AND  OF  GOUTY 
CONDITIONS. 

CHAPTER    XII. 
ACUTE    AND   CHRONIC    GOUT:    TREATMENT   AND   DIET. 

General  principles  of  treatment — Examination  of  the  urine — 
Treatment  of  acute  gout — The  action  of  colchicum — Diet 
in  acute  gout — Treatment  of  subacute  and  chronic  gout — 
Preventive  treatment  of  gout — Local  treatment  of  gouty- 
joints  —  Electric  light  and  superheated-air  baths — Cata- 
phoresis. 

General  principles  on  which  the  treatment  of  gout 
is  based. — In  the  first  place  it  should  be  borne  in  mind 
that  no  routine  treatment  can  be  adopted  which  is  suit- 
able to  all  cases.  The  nutritional  condition  of  the  patient, 
his  habits,  surroundings,  and  mode  of  life  constitute 
factors  that  must  necessarily  modify  the  treatment  of 
individual  cases,  and  with  gout,  as  with  so  many  other 
diseases,  it  will  be  found  that  each  individual  case  requires 
separate  study,  and  frequently  special  treatment.  Quite 
apart  from  the  treatment  of  an  attack  of  gout,  which  is 
a  comparatively  simple  and  easy  matter,  must  be  con- 
sidered the  treatment  of  the  condition  or  conditions  which 
led  up  to  the  attack.  In  connection  with  this  point  it 
must  be  remembered  that  the  gouty  individual  is  one 
whose  general  metabolism  is  unstable,  and  that  this  in- 
stabihty  may  be  present  in  one  or  more  of  the  great 
physiological   systems  —  the    digestive,    the   nervous,    the 

215 


2i6  GOUT:    TREATMENT.  [Parxiv. 

circulatory,  etc.  The  question  which  of  these  systems  is 
primarily  and  mainly  at  fault  should  always  be  a  matter 
for  patient  investigation,  and  one  must  then  endeavour 
to  improve  the  metabolism  of  that  system  by  suitable 
medicinal,  dietetic,  and  hygienic  treatment. 

The  treatment  of  gout  should  have  for  its  aim  the 
following  objects  : — (i)  The  treatment  of  the  gouty 
paroxysm  in  cases  of  acute  gout,  and  the  relief  of  the 
pain  as  speedily  as  possible  ;  (2)  the  treatment  of  the 
subacute  or  the  chronic  condition,  and  prevention  of 
the  recurrence  of  an  attack  ;  (3)  the  treatment  of  the 
affected  joint,  or  joints,  with  the  object  of  removing  the 
uratic  deposits,  and  of  preventing  permanent  deformity  ; 
and  (4)  the  treatment  of  the  various  forms  of  irregular 
or  abarticular  gout. 

Examination  of  the  urine. — In  all  cases  of  gout  a 
very  careful  examination  of  the  urine  should  be  made. 
The  indications  that  the  kidneys  are  not  performing  their 
proper  functions  are  the  existence  of  a  certain  amount 
of  polyuria,  a  low  specific  gravity  of  the  urine — usually 
from  1007  to  1016 — the  presence  of  a  small  quantity  of 
albumen,  which,  however,  may  disappear  for  some  time 
and  then  reappear,  the  presence  of  a  few  granular  casts 
if  a  careful  microscopical  examination  is  made  after  centri- 
fugalising  the  urine,  and  a  diminished  daily  excretion  of 
uric  acid  and  generally  of  urea.  It  is  most  important  care- 
fully to  examine  the  urine  for  traces  of  albumen,  and 
for  the  presence  of  casts.  For  the  latter  purpose  the 
centrifugal  machine  should  be  used,  as  the  casts,  when 
present,  are  usually  present  in  but  small  numbers,  and 
are  otherwise  very  slow  to  settle.  This  examination  for 
casts  should  always  be  made  in  those  cases  where  there 
is  a  suspicion  of  organic  renal  disease,  even  though  there 
may  be  a  complete  absence  of  albuminuria.  It  is  a  common 
occurrence  to  find  gouty  individuals  with  marked  signs 
of  renal  inadequacy  passing  urine   of  fairly  low  specific 


CHAP.xii]       TREATMENT    OF    ACUTE    GOUT.  217 

gravity  and  quite  free  from  albumen,  but  in  such  cases  a 
careful  examination  of  the  urine  will  always  reveal  the 
presence  of  granular  and  frequently  hyaline  casts. 

It  is  desirable  before  commencing  treatment,  and  from 
time  to  time  during  treatment,  to  know  the  amount  of 
uric  acid  that  is  being  daily  eliminated  in  proportion  to 
the  body-weight  of  the  patient.  This  determination  of 
the  amount  of  uric  acid  eliminated  must  be  made  on  a 
sample  of  the  mixed  urines  of  twenty- four  hours.  The 
mere  determination  of  the  percentage  of  uric  acid  in  a 
sample  of  the  urine  is  useless,  as  it  constitutes  no  guide 
to  the  actual  amount  of  uric  acid  that  is  being  excreted. 
It  is  absolutely  necessary  to  determine  the  total  uric  acid 
elimination  for  the  twenty-four  hours,  and  that  can  only 
be  done  by  examining  a  sample  of  the  mixed  urines  of 
that  period.  Similarly  the  determination  of  the  percentage 
of  urea  in  a  sample  of  the  urine  is  no  guide  to  the  amount 
of  nitrogenous  elimination  that  is  taking  place  from  the 
kidneys.  To  ascertain  that  factor  the  total  output  of 
urea  for  the  twenty-four  hours  must  also  be  determined. 

Treatment  of  acute  gout. — In  order  to  arrest  the 
abnormal  intestinal  fermentation,  to  remove  the  excessive 
numbers  of  intestinal  bacteria,  and  to  relieve  the  catarrh 
of  the  intestinal  mucosa,  all  factors  in  the  development 
of  abnormal  intestinal  toxins,  the  bowels  should  be  freely 
opened  with  four  grains  of  calomel  or  "  blue  pill,"  followed 
by  a  saline  aperient.  For  the  first  twenty-four  hours 
it  is  preferable  that  no  food  should  be  taken,  but  water 
should  be  drunk  freely. 

For  the  treatment  of  the  gouty  paroxysm  the  limb 
should  be  placed  in  the  horizontal  position,  or  slightly 
elevated  above  the  level  of  the  body,  and  a  cradle  should 
be  arranged  so  as  to  take  the  weight  of  the  bed-clothes 
from  the  affected  part.  To  alleviate  the  severe  pain  felt 
in  the  affected  joint,  warm  packs  should  be  arranged  round 
it,    consisting   of   cotton-wool   saturated   with   a   soothing 


2i8  GOUT:    TREATMENT.  [Parxiv. 

lotion,  and  then  lightly  covered  with  oil-silk,  I  have 
found  the  following  lotion  most  useful  in  relieving  the 
local  pain  : — 

Sodii  Carb.  .  .  .  .  .  •  5  "J- 

Linim.  Belladonnae  .  .  .  .  .  §  ij. 

Tinct.  Opii  .  .  .  .  .  .  ^  ij. 

Aq.   ad  .......  3  viij. 

A  small  portion  of  the  lotion  should  be  mixed  with  an 
equal  quantity  of  hot  water,  and  then  poured  on  cotton- 
wool previously  arranged  round  the  joint.  The  pack  should 
be  changed  every  four  hours.  In  connection  with  the 
acute  paroxysm,  no  attempt  at  local  depletion,  such  as 
the  application  of  leeches  to  the  inflamed  joint,  blistering, 
or  incisions,  should  on  any  account  be  made,  owing  to 
the  great  liability  of  thereby  extending  the  inflammatory 
condition,  and  so  producing  subsequent  ankylosis  or 
deformity. 

For  the  internal  treatment  of  acute  gout,  colchicum 
is  one  of  the  most  valuable  drugs  that  we  possess.  It 
should  be  especially  used  for  acute  gout,  and  for  subacute 
attacks  supervening  on  chronic  gout.  If  it  is  used  con- 
tinuously, tolerance  is  apt  to  be  acquired,  and  then  the 
drug  ceases  to  act.  At  the  commencement,  a  large  dose 
of  thirty  to  forty  minims  of  colchicum  wine  should  be 
given,  followed  by  a  mixture  containing  in  each  dose 
fifteen  to  twenty  minims  of  the  wine,  with  from  forty  to 
sixty  grains  of  citrate  of  potassium,  which  should  be  admin- 
istered three  times  a  day.  The  citrate  of  potassium,  which 
is  given  for  its  combined  properties  of  acting  as  a  diuretic 
and  of  diminishing  the  acidity  of  the  urine,  may,  if  desired, 
be  given  as  an  effervescing  mixture,  using  thirty  grains 
of  potassium  bicarbonate  to  twenty  grains  of  citric  acid. 
Colchicum  reduces  the  gouty  inflammation,  relieves  the 
pain,  and  shortens  the  attack.  It  should  only  be  taken 
under  medical  advice,  and  should  never  be  given  in 
such  doses   as  to  produce   extreme  depression  ;    after  the 


CHAr.xii]  COLCHICUM    AND    GOUT.  219 

inflammation  of  an  acute  attack  has  subsided,  the  doses 
of  colchicum  should  be  gradually  diminished  until  the  drug 
is  left  off.  A  very  useful  method  of  administering  col- 
chicum is  in  the  form  of  its  active  principle,  colchicine, 
which  may  be  given  in  doses  of  one-fiftieth  to  one-eightieth 
of  a  grain  three  or  four  times  a  day  immediately  after  food. 
Only  a  few  patients  will  tolerate  doses  of  one-fiftieth  of  a 
grain,  the  contra-indication  of  such  a  dose  being  the  pro- 
duction of  diarrhoea  and  intestinal  griping.  The  following 
constitutes  a  very  useful  pill  : — 


Colchicinae     . 
Ext.  Nucis  Vom. 
Ext.   Hyoscyami 
Ext.  Gentianae 


gr.  k 


IT. 


2" 


gr-  ]■ 


After  the  initial  free  purgation,  as  previously  mentioned, 
it  is  not  desirable  to  produce  too  free  an  action  of  the 
bowels.  All  that  is  necessary  is  to  have  a  sufficient  action 
to  relieve  portal  congestion  and  intestinal  catarrh.  The 
following  pill  effects  this  purpose,  in  most  cases,  very  well. 
It  is  administered  at  night,  and  is  followed  up,  when  neces- 
sary, by  a  dose  of  saline  in  the  morning. 

Leptandrin             .  .  .  .  .  .  gr.  j. 

Iridin              .           .  .  .  .  .  .  gr.  j. 

Ext.   Hyoscyami    .  .  .  .  .  .  gr.  j. 

Ext.  Colocynth  Co.  .  .  .  .  .  gr.  ij. 

If  the  pain  of  an  acute  attack  of  gout  is  so  severe  as 
to  prevent  sleep,  seven  grains  of  veronal,  or  ten  grains  of 
trional  may  be  given,  or  a  full  dose  of  extract  of  hyoscyamus 
will,  in  some  cases,  act  as  a  very  useful  anodyne.  The 
administration  of  opium  or  morphine  should,  if  possible, 
be  avoided  owing  to  the  risk  of  its  deficient  elimination, 
and  also  on  account  of  its  diminishing  the  amount  of  urine, 
and  its  tendency  to  derange  digestion  and  to  check  hepatic 
metabolism. 

Action  of  colchicum. — For  the  past  few  years  my 
thoughts    have    been     directed    with    increasing    intensity 


220  GOUT:    TREATMENT.  [Partiv. 

to  the  view  that  the  intestinal  tract  is  a  very  powerful 
factor,  if  not  the  primary  factor,  in  the  development  of 
gout.  My  attention  was  first  directed  to  this  view  as  the 
result  of  some  clinical  observations  which  I  was  making 
in  an  attempt  to  explain  the  action  of  colchicum  in  cases 
of  gout.  I  happened  at  that  time  to  see  some  cases  of 
acute  colchicum  poisoning,  which  in  many  respects  re- 
sembled acute  arsenical  poisoning. 

In  toxic  doses,  colchicum  is  first  a  gastro-intestinal 
irritant ;  it  produces  nausea,  vomiting,  choleraic  diarrhoea, 
and  rice-water  stools,  just  as  arsenical  poisoning  does. 
It  also,  in  sufficient  toxic  doses,  produces  cardiac  depression, 
and  a  bilateral  neuritis,  similar  to  that  produced  by  arsenic. 
If,  then,  in  therapeutic  doses,  the  main  action  of  colchicum 
is  upon  the  gastro-intestinal  canal,  its  rapid  efficacy,  in 
cases  of  gout,  is  possibly  due  to  its  effect  upon  those  abnormal 
intestinal  changes  which  constitute  the  primary  factor 
in  that  disease.  Colchicum  increases  the  secretion  from 
the  intestinal  mucous  membrane,  and  so  either  prevents 
the  formation,  or  effects  the  destruction,  of  the  intestinal 
toxin  which,  when  absorbed  into  the  circulation,  is  re- 
sponsible for  the  development  of  gout. 

It  is  probable  that  the  drugs  that  are  of  most  value  in 
the  treatment  of  gout  owe  their  efficacy  chiefly  to  their 
power  of  checking  intestinal  putrefaction,  as  well  as  to 
preventing  the  absorption  or  promoting  the  elimination 
of  the  products  of  such  intestinal  putrefaction. 

Diet  in  acute  gout. — As  previously  mentioned,  it 
is  preferable  that  no  food  be  taken  for  the  first  twenty- 
four  hours  of  an  acute  attack  of  gout,  but  water  should 
be  drunk  freely.  During  the  acute  attack  the  patient  should 
be  restricted  to  a  milk  diet,  which  may  consist  of  milk, 
bread  and  milk,  and  tea  made  with  boiling  milk  instead 
of  with  water.  Weak  tea  with  cold  toast  thinly  buttered 
may  also  be  taken.  The  free  drinking  of  hot  or  cold  water, 
of  salutaris  water,  or  of  some  simple  mineral  water,  should 


CHAr.xii]     TREATMENT    OF   CHRONIC   GOUT.  221 

be  encouraged.  The  milk  diet  should  be  continued  until 
the  acute  inflammation  is  subsiding,  which  stage  is  indi- 
cated by  the  lessening  of  the  pain,  and  by  the  pitting  on 
pressure  of  the  affected  parts.  No  alcohol  in  any  form 
should  be  given  during  this  stage,  unless  there  are  strong 
reasons  for  its  administration,  such  as  a  weak  action  of 
the  heart  and  a  feeble,  irregular  pulse,  when  a  little  well- 
matured  whisky  diluted  with  salutaris  water  will  prove 
the  best  form  of  alcohol.  Beef  tea  and  any  of  the  meat 
extracts  or  essences  should  be  avoided  at  all  times  by 
gouty  patients,  owing  to  the  tendency  they  have  to  irritate 
the  kidneys,  and  to  the  fact  that  they  are  loaded  with 
waste  nitrogenous  products.  With  the  subsidence  of  the 
acute  attack  the  patient  may  return  to  a  more  liberal  diet, 
but  care  should  be  taken  to  avoid  anything  indigestible. 
The  dietary  suitable  for  gouty  subjects  after  the  acute 
attack  has  subsided  is  fully  dealt  with  in  the  chapter  on 
diet  in  gout. 

Treatment  of  subacute  and  chronic  g-out.  —  In 
addition  to  colchicum,  which  may  be  given  in  small  doses, 
guaiacum  may  very  usefully  be  administered  as  an  alter- 
ative which  stimulates  the  metabolism  of  the  liver,  and 
also  affords  relief  to  the  portal  system.  From  five  to  ten 
grains  of  guaiacum  resin  should  be  given  in  cachets  two 
or  three  times  a  day,  according  to  the  effect  on  the  bowels, 
since  guaiacum  sometimes  acts  as  a  laxative.  The  method 
of  administering  the  powdered  guaiacum  resin  in  cachets 
is  far  preferable  to  giving  the  tincture  of  guaiacum  in  a 
mixture,  as,  in  the  latter  form,  a  nauseous  medicine  is 
produced,  and  the  precipitated  resin  tends  to  cling  obstin- 
ately to  the  tongue  and  fauces.  In  cases  of  chronic  gout, 
the  colchicum  may  be  very  conveniently  administered  in 
the  form  of  the  colchicine  pill,  given  three  times  a  day. 
In  order  to  encourage  the  elimination  by  the  kidneys  of 
the  toxic  agents  of  gout,  citrate  or  bicarbonate  of  potassium 
should  be  employed  as  a  diuretic,  which  increases  the  volume 


222  GOUT:    TREATMENT.  [Partiv. 

of  the  urine,  and,  at  the  same  time,  diminishes  its  acidity. 
The  use  of  the  potassium  salt  may  with'  advantage  be 
pushed  until  moderate  alkalinity  of  the  urine  is  produced, 
as,  by  such  means,  the  tendency  to  the  deposition  of  uric 
acid,  or  sodium  biurate,  in  the  kidney-tissues  is  removed. 
Free  diuresis  should  also  be  encouraged  by  the  drinking 
of  sufficient  quantities  of  water.  Of  the  beneficial  effects 
of  employing  a  potassium  salt  in  conjunction  with  col- 
chicum  in  the  treatment  of  acute  and  subacute  gout  I 
am  fully  assured,  and  my  experience  is  that,  of  the  various 
potassium  salts,  the  citrate  is  the  most  useful.  If  given 
in  sufficiently  large  doses,  it  tends,  by  its  conversion  in 
the  kidneys  into  the  carbonate,  to  diminish  the  acidity 
of  the  urine,  which  is  generally  high  in  connection  with 
the  gouty  paroxysm,  while,  at  the  same  time,  it  increases 
the  solvent  power  of  the  urine  for  the  uric  acid  salts,  and 
so  assists  their  elimination.  In  cases  of  sluggish  action 
of  the  liver,  of  gastro-intestinal  catarrh  and  torpor,  of 
gouty  dyspepsia,  and  of  other  forms  of  irregular  gout,  in 
which  there  are  no  appreciable  uratic  deposits  in  the  joints, 
mineral  waters  containing  sodium  salts  are  undoubtedly 
beneficial,  owing  to  the  action  of  those  salts  as  hepatic 
and  gastro-intestinal  stimulants. 

As  regards  the  use  of  lithium  salts  in  the  treatment  of 
gout,  my  opinion  is  that  they  are  not  so  useful  as  the 
potassium  and  sodium  salts.  The  principal  objection  to 
their  use  is  their  greater  toxicity,  and  depressing  action 
on  the  heart,  as  compared  with  the  potassium  salts.  They 
consequently  have  to  be  given  in  such  small  doses  that  I 
am  very  doubtful  whether,  in  such  doses,  they  possess 
any  remedial  effect  at  all.  On  the  other  hand,  I  constantly 
meet  with  patients  suffering  from  cardiac  depression,  and 
even  dilatation,  as  the  result  of  the  excessive  and  continued 
consumption  of  lithia  tablets,  which  are  so  persistently,  so 
speciously,  and  so  wrongly  vaunted  as  curative  of  gout. 

The  enlargement  and  tenderness  of  the  gouty  joints  is 


Chap.  XII.]     TREATMENT    OF    CHRONIC    GOUT.         223 

due  to  two  causes,  the  deposition  of  sodium  biurate  in  the 
cartilages  and  fibrous  structures,  and  a  chronic  inflamma- 
tory thickening  of  the  fibrous  tissues.  For  the  reduction 
of  this  thickening,  as  well  as  for  painful  gout  of  the  sole 
of  the  foot,  and  for  gouty  neuralgic  affections,  iodide  of 
potassium,  given  internally,  is  a  useful  remedy.  In  cases 
of  gout  associated  with  the  contracted  granular  kidney, 
as  evidenced  by  slight  albuminuria  and  high  arterial  tension, 
the  administration  of  iodide  of  potassium  is  also  most 
beneficial.  I  usually  prescribe  it  in  doses  of  ten  grains 
three  times  a  day,  and  continue  its  use  over  a  period  of 
six  or  eight  weeks.  My  experience  is  that  it  seems  to  act 
more  beneficially  when  given  in  combination  with  the 
compound  decoction  of  sarsaparilla. 

In  the  treatment  of  the  gouty  state  associated  with 
disturbance  of  the  functions  of  the  liver,  the  most  important 
consideration  is  the  restoration  of  that  organ  to  its  normal 
state  of  activity,  and  here  the  alkaline  sodium  salts  are 
especially  useful.  There  is  no  better  treatment  at  the 
outset  than  a  dose  of  blue  pill  or  calomel  at  night,  followed 
by  a  dose  of  Epsom  salts  or  Carlsbad  salts  in  the  morning. 
Subsequently  a  pill  containing  a  small  dose  of  "  blue  pill  " 
or  calomel  combined  with  euonymin  and  colocynth  will 
be  found  most  useful.  In  such  cases  of  gouty  hepatic 
inadequacy  a  mixture  which  I  have  found  most  beneficial 
as  regards  its  stimulating  effect  on  the  metabolism  of  the 
liver,  and  also  of  the  gastro-intestinal  tract,  is  one  containing 
sodium  bicarbonate,  gentian,  and  nux  vomica,  taken  a 
quarter  of  an  hour  before  meals. 

The  indulgence  in  high  living  by  gouty  subjects  induces 
arterial  plethora  and  a  rise  of  blood  pressure.  The  conse- 
quent strain  on  the  arterial  walls  produces  arterial  disease 
if  continued  long  enough,  but  in  the  early  stages  of  such  rise 
in  blood  pressure  the  administration  of  "blue  pill"  and  careful 
attention  to  diet  will  always  prevent  the  incidence  of  arterial 
disease.     Gouty  subjects  are  more  prone  to  the  injurious 


224  GOUT:    TREATMENT.  [Partiv. 

effects  of  constipation  of  even  a  slight  degree  than  non-gouty 
individuals. 

So-called  "  Solvents  of  uric  acid," — Uric  acid  can- 
not be  "  washed  out  "  of  the  system.  Substances  that 
dissolve  uric  acid  in  the  test  tube  are  of  little  or  no  use 
in  increasing  the  output  of  uric  acid  in  the  body.  When 
drugs  do  increase  or  diminish  the  uric  acid  excretion,  they 
act  by  directly  affecting  the  cellular  processes  of  the  body, 
and  not  by  dissolving  out  the  uric  acid  deposits.  In  no 
case  is  there  a  possibility  of  converting  the  uric  acid  in 
the  deposits  into  a  more  soluble  condition  by  the  addition 
of  potassium  or  lithium  salts.  The  only  possibility  of 
converting  a  sparingly  soluble  primary  urate  into  a  more 
soluble  compound  is  to  remove  the  primary  uric  acid  ions 
from  the  solution.  That  can  be  done  by  addition  of  strong 
alkaline  solutions  which  convert  the  primary  uric  acid  ions 
into  secondary  ions  ;  but  that  is  obviously  a  method  in- 
applicable in  therapeutical  practice. 

Some  years  ago  a  solvent  of  uric  acid  seemed  to  have 
been  found  in  urea.  It  was  apparently  shown  by  Rudel 
that  a  water  solution  of  urea,  as  well  as  urine,  would  dissolve 
very  considerable  quantities  of  uric  acid  or  urates.  One  litre 
of  a  2  per  cent,  urea  solution  was  said  to  dissolve  at  the 
normal  temperature  about  0"5  gramme  of  uric  acid,  and  a 
10  per  cent,  solution  more  than  2  grammes,  while  a  litre  of 
water  dissolves  only  0.0253  gramme.  Moreover,  compounds 
of  the  urea  with  uric  acid  were  said  to  have  been  isolated, 
and  these  observations  excited  much  interest  in  regard  to 
the  treatment  of  gout  and  stone  formation.  Careful  repe- 
tition of  Rudel's  experiments  has,  however,  led  to  directly 
opposite  conclusions,  and  it  may  be  confidently  stated  that 
urea  does  not  affect  the  solubility  of  uric  acid  in  water. 
Neither  does  its  presence  in  a  water  solution  sensibly  counter- 
act the  separation  of  uric  acid  from  its  salts.  Nor  could 
any  compounds  of  uric  acid  and  urea  be  obtained.  Con- 
sequently, since  urea  has  no  influence  upon  the  relations 


CHAP.  XII.]         .  PREVENTIVE    TREATMENT.  225 

of  solubility  and  equilibrium  of  uric  acid  or  its  salts,  the 
proposed  treatment  with  urea  is  destitute  of  any  scientific 
foundation. 

I  have  deemed  it  advisable  to  make  no  reference  to 
the  employment  of  any  of  the  numerous  preparations 
which  are  so  constantly  being  introduced  to  our  notice  as 
infallible  solvents  of  uric  acid,  and  as  specifics  for  gout. 
It  is  not  that  I  have  not  made  trial  of  them,  but  such  trials 
have  always  led  to  disappointment,  and  have  sent  me  back 
with  renewed  confidence  to  the  drugs  of  our  Pharmacopoeia. 
I  have  witnessed,  and  doubtless  shall  again  witness,  the 
rise  and  fall  in  popularity  of  many  a  so-called  solvent  of 
uric  acid,  which  has  been  introduced  with  exaggerated 
praise,  and  with  the  usual  undeserved  laudation  born  of 
insufficient  experience. 

Preventive  treatment  of  gout. — After  convalescence, 
as  much  exercise  as  possible,  short  of  fatigue  and  discomfort, 
should  be  taken  in  the  open  air.  Cycling  is  an  excellent 
exercise  for  the  gouty,  since  it  furnishes  good  muscular 
movement  in  the  open  air  without  the  gouty  joints  having 
to  bear  the  weight  of  the  body. 

I  have  now  had  a  considerable  experience  of  the  pro- 
phylactic effects  of  guaiacum  resin,  and  I  must  confess  that 
I  know  of  no  drug  which  is  more  useful  in  the  preventive 
treatment  of  gout.  Its  action  is  probably  due  to  its  stimu- 
lating effect  on  intestinal  and  hepatic  metabolism.  The 
form  in  which  I  prefer  to  give  it  is  that  of  the  powdered 
resin  in  cachets,  commencing  with  doses  of  5  grains  three 
times  a  day  after  meals,  and  gradually  increasing  the  dose 
to  one  of  10  or  12  grains.  In  this  form  it  can  be  taken 
without  any  discomfort  to  the  patient,  whereas  if  admin- 
istered in  the  form  of  the  tincture  in  a  mixture  a  most 
nauseousl'medicine  results. 

To  prevent,  as  far  as  possible,  the  recurrence  of  gout 
the  patient  should  also  give  careful  attention  to  diet  on 
the  fines  laid  down  in  the  chapter  on  diet.     Regular  habits 


226  GOUT:    TREATMENT.  [Partiv. 

of  life,  with  even  and  sufficient  exercise,  should  be  encour- 
aged, and  constipation  should  be  zealously  avoided. 

Briefly  stated,  the  individual  who  is  subject  to  gout, 
and  who  wishes  to  prevent  a  recurrence  of  the  disease, 
should  lead  an  active  and  an  abstemious  life. 

Local  treatment  of  gouty  joints. — If  much  swelling 
of  a  joint  persists,  the  limb  should  be  elevated  as  much  as 
possible,  and  a  light  flannel  bandage  applied  to  the  joint. 
If  the  oedema  persists,  the  hot  douche  followed  by  sponging 
with  a  cold  strong  solution  of  common  salt  will  be  found 
serviceable.  The  application  of  the  so-called  solvents  of 
uric  acid  externally  to  affected  joints  is  useless,  as  they  are 
not  solvents  of  sodium  biurate.  Careful  massage  and  gentle 
exercise  of  the  stiffened  joints  should  be  employed,  but  only 
when  convalescence  is  fairly  established  ;  massage  and 
muscular  movement  increase  the  flow  of  lymph  in  the  lymph 
channels,  and  so  tend  to  promote  the  removal  of  uratic 
deposits,  and  to  increase  general  metabolism. 

A  free  movement  of  the  lymph  in  the  lymph  channels 
is  essential  to  oxidation  and  metabolism,  and  therefore 
massage  and  muscular  movements  exercise  an  important 
influence  on  account  of  the  pumping  action  produced  in 
the  lymph-spaces  by  both  forms  of  exercise.  Muscular 
movements  and  respiration  are  almost  the  only  means  by 
which  the  circulation  is  ordinarily  carried  on  in  this  system, 
as  it  has  no  motor  mechanism  with  the  exception  of  the 
vis-a-tergo  of  the  heart  and  arteries,  and,  if  these  latter 
are  in  default,  delay  and  defective  metabolism  must  result 
if  muscular  exercise  is  not  taken.  This  is  an  argument, 
from  the  physiological  side,  in  proof  of  the  fact  that  a 
sedentary  life  and  deficient  exercise  conduce  to  gout. 
Massage  should  never  be  resorted  to  in  cases  of  acute  gout, 
as  it  not  only  aggravates  the  disease  at  that  stage,  but 
also  causes  severe  pain  ;  it  should  be  reserved  for  the  more 
chronic  cases.  Massage  produces  an  increase  in  the  amount 
of  blood  and  lymph  passing  through  the  tissues  concerned, 


cHAP.xii.j  TREATMENT    OF    JOINTS.  227 

at  the  time  and  afterwards.  This  improves  the  nutrition 
of  the  affected  tissues,  promotes  absorption  of  deposits, 
and  restores  physiological  activity.  In  subacute  or  chronic 
cases,  where  the  joints  remain  swollen  and  cedematous, 
and  are  the  seat  of  considerable  deposits,  much  benefit  is 
frequently  derived  from  massage  and  galvanism.  Each  of 
the  affected  joints  should  be  massaged  for  a  few  minutes, 
and  then  galvanism  (5  to  10  milliamperes)  applied  for  a 
few  minutes  with  the  negative  pole  over  the  affected  region, 
to  be  again  followed  by  massage.  Under  this  combined 
treatment  the  oedema  and  deposits  frequently  disappear 
rapidly.  Probably  the  beneficial  effects  are  due  mainly 
to  the  increased  circulation  of  blood  and  lymph  induced, 
and  the  consequent  absorption  that  takes  place. 

The  Scotch  douche  is  very  useful  in  the  treatment  of 
chronically  affected  joints.  A  good-sized  stream  is  thrown 
with  considerable  force  upon  the  affected  joint,  cold  water 
being  first  employed  for  half  a  minute,  and  then  hot ;  the 
latter  should  be  as  hot  as  the  patient  can  bear,  and  should 
be  continued  for  one  minute.  This  process  is  repeated  for 
fifteen  or  twenty  minutes.  The  repeated  alternations  of 
temperature  produce  a  stimulating  effect  upon  the  circula- 
tion about  the  joint,  and  so  increase  tissue  change,  and 
favour  absorption.  Massage  of  the  joint  should  be  resorted 
to  immediately  after  the  douching,  as  the  tissues  are  then 
in  a  relaxed  condition.  In  many  cases  of  chronic  articular 
gout  the  salt  pack  is  efficacious.  It  consists  of  flannel 
soaked  in  a  warm  saturated  solution  of  common  salt,  which 
is  wrapped  round  the  affected  joint,  covered  with  oiled 
silk  and  a  bandage,  and  kept  on  all  night.  It  should  be 
repeated  nightly  as  necessary. 

For  the  stiffness  and  thickening  of  joints,  careful  rubbing 
with  iodide  of  potassium  and  soap  liniment  or  with  the 
compound  camphor  liniment  may  be  resorted  to.  The 
thermal  baths  of  Bath,  Buxton,  Harrogate,  Strathpeffer, 
Llandrindod    Wells,    Aix-les-Bains,     and    other    spas    and 


228  GOUT:    TREATMENT.  [partiv. 

mud-baths,  are  useful  in  the  treatment  of  cases  of  chronic 
articular  gout.  Treatment  by  means  of  baths  should, 
however,  be  avoided  by  patients  suffering  from  acute  gout, 
by  elderly  patients,  and  by  those  suffering  from  any  serious 
cardiac  affection. 

Electric  lig-ht  and  superheated-air  baths. — I  have 
found  in  many  cases  that  a  decidedly  beneficial  influence 
on  gouty  joints  is  produced  by  electric  light  baths,  followed 
by  electrical  treatment  in  the  form  of  cataphoresis  to  the 
affected  joints. 

Electric  light  and  superheated-air  baths  promote  the 
oxidative  processes  within  the  body,  as  is  shown  by  the 
increased  elimination  of  carbon  dioxide  from  the  lungs,  and 
also  by  the  increased  metabolism  of  the  body  in  general. 
They  also  stimulate  the  circulation  of  both  the  blood  and  the 
lymph  in  the  affected  joints  and  so  lead  to  improved  nutri- 
tion of  the  parts.  This  curative  action  undoubtedly  con- 
tinues after  the  treatment  has  been  left  off.  Such  treatment 
therefore  is  better  given  intermittently — say,  six  baths  on 
alternate  days  ;  then  intermit  for  two  or  three  weeks  and 
so  on.  These  baths  improve  the  atrophic  condition  of  the 
muscles.  They  cause  a  temporary  elevation  of  the  body- 
temperature,  marked  reddening  of  the  skin  of  the  part 
treated,  profuse  local  or  even  general  perspiration,  quickened 
pulse,  lowered  arterial  tension,  and  generally  considerable 
amelioration  of  the  pain,  and  in  some  cases  complete  dis- 
appearance of  it  for  a  time.  Radiant  heat  has  a  greater 
penetrative  effect  than  other  forms  of  heat,  and,  in  my 
opinion,  the  effect  is  more  stimulating.  In  cases  of  acute 
or  subacute  gout  the  pain,  as  a  rule,  recurs  at  varying 
intervals  after  a  bath,  but  usually  with  diminished  severity  ; 
and  in  favourable  cases  a  progressive  reduction  of  the  pain 
occurs  after  the  use  of  subsequent  baths. 

Undoubtedly  many  cases  of  chronic  gout  do  not  show 
much  improvement  after  the  use  of  electric  light  or  super- 
heated-air baths,  and  I  have  frequently  experienced  great 


Chap.  XII.]  ELECTRIC    LIGHT    BATHS.  229 

difficulty  in  selecting  the  cases  most  likely  to  be  benefited 
by  it.  As  a  general  rule  my  experience  "has  been  that  cases 
of  chronic  gout  of  long  standing,  with  considerable  deposits 
in  the  joints,  do  not  derive  much  benefit  from  these  baths. 
For  such  cases  undoubtedly  much  more  good  can  be  done 
by  the  employment  of  vapour  baths,  followed  by  massage 
of  the  affected  joints,  a  method  of  treatment  which  is 
frequently  most  useful  in  producing  softening  and  absorption 
of  the  deposits.  It  should,  however,  be  borne  in  mind 
that  electric  light  baths  seem  to  set  up  improved  circulatory 
and  trophic  changes  in  the  joints,  which  apparently  are 
maintained  for  a  prolonged  period  after  the  baths  have 
been  discontinued.  Certainly  I  have  seen  in  several  cases, 
after  a  course  of  twelve  to  eighteen  electric  light  baths 
had  resulted  in  but  slight  improvement,  and  the  baths  had 
been  abandoned  in  despair,  a  progressive  improvement 
maintained  for  weeks  and  even  months  after  the  discon- 
tinuance of  the  baths,  an  improvement  which  in  some 
cases  has  issued  in  more  or  less  complete  cure. 

If  only  one  limb  is  the  seat  of  gout,  the  question  arises 
as  to  whether  that  limb  should  be  locally  treated  by  being 
placed  in  a  small  specially-constructed  bath,  or  whether 
the  "  entire  body  "  bath  should  be  used.  My  experience 
is  that  the  "  whole  body  "  bath  is  in  all  cases  the  most 
useful,  with,  in  the  case  of  the  electric  light  bath,  an  extra 
localisation  of  the  heat  and  light  rays  on  the  affected  part. 
That  means,  according  to  my  experience,  that  the  more 
extensive  the  surface  to  which  the  heat  and  light  rays  are 
applied  the  better  is  the  result.  When  the  ordinary  electric 
light  or  superheated-air  baths  are  not  obtainable,  very  good 
results  may  be  obtained  at  home  by  the  use  of  an  ordinary 
blanket-tent  with  a  small  opening  at  the  top  to  let  out  the 
hot  air  saturated  with  moisture.  The  hot  air  is  supplied 
by  a  ring  bunsen  gas-burner,  or  by  a  large  spirit-lamp 
with  a  flue  passing  through  an  opening  in  the  blanket  at 
the  foot  of  the  tent. 


230  GOUT:    TREATMENT.  ipartiv. 

In  the  acute  or  subacute  stage  of  gout,  or  when  a  shght 
attack  of  gout  has  just  started,  I  consider  the  use  of  the 
Turkish  bath  most  undesirable.  I  have  known  of  its  em- 
ployment in  such  cases  being  followed  by  an  exacerbation 
of  the  attack  and  extension  to  joints  not  at  the  time  affected. 
This  is  a  point  which  should  be  borne  in  mind  by  medical 
men,  as  many  patients  on  the  first  appearance  of  an  attack 
of  gout  are  apt  to  have  immediate  recourse  to  the  Turkish 
bath,  and  it  is  well  that  they  should  be  warned  of  the  danger 
they  thereby  incur. 

Cataphoresis. — Cataphoresis  is  useful  in  many  cases 
of  chronic  gout  with  considerable  deposits  in  the  joints. 
By  cataphoresis  is  meant  electric  osmosis,  or  the  transfer 
through  porous  partitions  from  anode  to  cathode.  The 
joint  may  be  treated  either  by  immersion  in  a  local 
bath  of  the  fluid  which  is  to  be  introduced,  the  positive 
electrode  being  placed  in  the  bath  and  the  negative  on  the 
back,  or  the  positive  electrode  may  be  kept  thoroughly 
wet  by  frequent  applications  of  the  fluid.  The  negative 
electrode  should  be  a  large  one,  about  eight  inches  by  five 
inches,  made  of  zinc  and  protected  by  a  flannel  cover.  It 
is  well  moistened  with  warm  water,  and  applied  to  the 
lumbar  or  dorsal  region.  At  the  positive  pole  either 
potassium  bicarbonate  or  lithium  iodide  may  be  introduced 
into  the  affected  joint.  In  the  former  instance  the  positive 
electrode  is  kept  thoroughly  wet  with  a  saturated  solution 
of  potassium  bicarbonate  ;  in  the  latter  the  joint  is  painted 
over  with  iodine  liniment,  and  a  pad  of  lint  soaked  in  a 
saturated  solution  of  lithium  carbonate  is  laid  over  the 
iodine  surface  ;  on  the  lint  the  positive  electrode,  which 
should  be  a  large  flat  one,  is  placed,  and  closely  applied  to  it. 
Care  must  be  taken  to  have  everything  in  situ  before  turning 
on  the  current,  so  as  to  avoid  any  shock,  and  to  give  an 
easy,  steady  flow  of  current. 

Although  it  is  not  possible  to  absorb  gouty  deposits 
through  the  skin  by  means  of  alkaline  baths,  yet  it  seems 


Chap.  XII.]  CATAPHORESIS.  231 

probable  that  such  a  result  can  be  effected  by  means  of 
electrolysis.  Edison,  in  1890,  suggested  electrolysis  for  the 
introduction  of  lithium  into  gouty  tissues,  and  since  his 
time  several  medical  experimenters  have  noted  the  good 
effect  of  this  form  of  treatment.  More  recently  Bordier 
repeated  these  experiments,  also  using  as  electrode  a  bath 
containing  a  solution  of  lithium,  and  made  a  series  of  appli- 
cations to  a  patient  with  large  gouty  deposits  in  the  hands. 
He  was  not  only  able  to  demonstrate  the  presence  of  lithium 
in  the  patient's  urine,  as  had  been  done  before  by  others, 
but,  and  this  is  even  more  striking,  he  detected  the  presence 
of  uric  acid  in  the  liquid  of  the  arm  baths,  thus  proving  both 
the  introduction  of  the  cathion  lithium  and  the  extraction 
of  the  anion  uric  acid  at  one  operation.  There  was  also  a 
marked  change  for  the  better  in  the  condition  of  the  patient's 
gouty  deposits  as  a  result  of  the  experiments. 


CHAPTER    XIII. 

TREATMENT   OF   IRREGULAR   GOUT. 

The  treatment  of  the  various  forms  of  irregular  gout — Gouty- 
dyspepsia  —  Hyperchlorhydria  —  The  gouty  heart  —  Neuritis 
— Insomnia — Gouty  eczema — Gouty  glycosuria  and  diabetes 
— Retrocedent  or  Metastatic  Gout. 

Gouty  dyspepsia  and  acidity.  —  In  addition  to  the 
usual  remedies,  such  as  bismuth  subcarbonate,  sodium 
bicarbonate,  bitters,  etc.,  taka-diastase  is  a  most  useful 
drug  in  the  treatment  of  gouty  dyspepsia.  It  is  made  up 
in  the  form  of  tablets  containing  two  and  a  half  grains  in 
each  tablet,  and  one  of  these  should  be  taken  immediately 
before  each  meal.  The  taka-diastase  encourages  the 
digestion  of  the  carbohydrate  elements  of  the  food,  and 
so  prevents  the  development  of  fatty  acids,  which,  by  their 
irritating  effects,  are  so  common  a  factor  in  the  development 
of  gouty  dyspepsia. 

Hyperchlorhydria. — The  treatment  of  this  condition 
consists  in  a  proper  regulation  of  the  diet  by  cutting  off 
any  excess  of  the  proteid  articles  of  diet,  and  by  neutralising 
the  superfluous  acid  by  the  administration  of  some  alkali. 
A  drug  that  I  have  found  most  useful  in  the  treatment  of 
this  hyperchlorhydria  is  hopogan  (the  magnesium  peroxide). 
It  not  only  gives  immediate  relief  of  the  pain  and  discomfort 
by  its  neutralising  effect  on  the  excess  of  acid,  but  it  also 
parts  with  one-half  of  its  oxygen,  and  acts  as  an  internal 
antiseptic.  It  is  a  most  valuable  drug  in  many  abnormal 
gastric  and  intestinal  fermentations.  It  is  a  white  tasteless 
powder,  and  is  best  given  in  a  little  milk  in  doses  of  twenty 
to  thirty  grains  three  or  four  times  a  day  taken  one  hour 

232 


Chap.  XIII.] 


HEPATIC    TORPOR. 


233 


after  meals.  If  it  exerts  too  great  a  purgative  effect,  tlie 
dose  should  be  diminished.  It  is  also  very  useful  in  allaying 
the  irritation  in  many  cases  of  gouty  pruritus,  which  are 
probably  due  to  absorption  of  a  toxin  or  toxins  from  the 
intestinal  tract.  In  cases  of  ordinary  neurotic  dyspepsia, 
associated  with  flatulence,  the  drug  is,  in  my  experience, 
of  no  value  whatever. 

Hepatic  torpop. — A  very  common  form  of  irregular 
gout  is  due  to  defective  metabolism  of  the  liver,  and  is 
known  as  hepatic  torpor,  or  hepatic  inadequacy.  In  this 
form,  the  faeces  are  pale,  generally  very  offensive,  and,  as 
a  rule,  constipation  occurs.  Slight  jaundice  is  usually 
present,  as  evidenced  by  a  yellowish  conjunctiva  and 
muddy  complexion,  and  the  urine  is  highly  coloured,  of 
high  specific  gravity,  and  very  acid.  In  the  treatment  of 
this  form  of  irregular  gout  the  most  important  consideration 
is  the  restoration  of  the  liver  to  its  normal  state  of 
activity,  and  here  the  alkaline  sodium  salts  are  especially 
useful.  There  is  no  better  treatment  at  the  outset  than  a 
dose  of  "  blue  pill  "  or  calomel  at  night,  followed  by  a 
dose  of  Epsom  salts  or  Carlsbad  salts  in  the  morning. 
Subsequently,  a  pill  containing  a  small  dose  of  "  blue  pill  " 
or  calomel,  combined  with  euonymin  and  colocynth,  will 
be  found  most  useful.  In  such  cases  of  gouty  hepatic 
inadequacy  a  mixture  which  I  have  found  most  beneficial 
as  regards  its  stimulating  effect  on  the  metabolism  of  the 
liver,  and  also  of  the  gastro-intestinal  tract,  is  the  following, 
which  should  be  taken  a  quarter  of  an  hour  before  meals  : — 


Sodse  Bicarb. 

.    gr.  xij. 

Tinct.  Nucis.  Vom. 

n  X. 

Tinct.  Gentian  Co. 

.       5  ss. 

Sp.  Chloroformi    . 

.      n  xij. 

Aq.   Menth.  Pip. 

.     ad  5J. 

Gouty  heart  is  associated  with  fatty  degeneration  of 
the  cardiac  walls.  The  treatment  should  be  rest  in  the  re- 
cumbent position,  and  a  small  dose  of  "  blue  pill "  or  calomel. 


234  GOUT:    TREATMENT.  ipartiv. 

followed  by  a  purge  of  Epsom  salts,  should  be  administered. 
If  the  pulse  is  of  low  tension  a  mixture  containing  convallaria 
and  strychnine  will  be  suitable.  If  anginal  attacks  occur, 
nitroglycerine  or  erythrol  tetra-nitrate  may  be  given  by 
the  mouth,  or  inhalations  of  nitrite  of  amyl  employed. 
Iodide  of  potassium  is  also  a  very  useful  drug  when  there 
is  much  pain.  The  patient  must  be  carefully  dieted,  and 
graduated  exercise,  at  first  of  a  passive  nature,  such  as  the 
Schott  treatment,  and  later  of  an  active  nature,  may  be 
very  beneficial.  The  action  of  the  bowels  should  be  properly 
regulated,  and  entire  abstention  from  tobacco  smoking, 
or  extreme  moderation  in  its  use,  should  be  advised. 

The  anginal  and  syncopal  attacks  that  occur  in  connec- 
tion with  the  gouty  heart  do  not  prove  fatal,  but  care  must 
be  taken  not  to  overtax  the  heart,  and,  at  first,  only  gentle 
outdoor  exercise  on  the  level  should  be  allowed. 

Ang'ina  pectoris. — In  anginal  attacks  in  gouty  subjects 
the  pulse  is  generally  one  of  high  tension  without  the 
existence  of  any  necessary  association  of  atheroma  of  the 
vessels.  For  the  immediate  relief  of  the  actual  attacks 
nitroglycerine  is  the  best  drug  to  employ,  although  in  rare 
cases  nitrite  of  amyl  may  be  found  more  efficacious.  Stim- 
ulants and  morphine  administered  hypodermically  should 
also  be  employed  if  necessary.  For  some  days  after  an 
attack  nitroglycerine  in  doses  of  one-hundredth  of  a  grain 
should  be  given  two  or  three  times  a  day.  If  organic 
cardiac  mischief  exist,  the  condition  must  be  suitably 
treated  on  general  principles.  In  cases  of  anginal  attacks 
occurring  in  gouty  subjects,  as  soon  as  the  severe  pain  has 
been  relieved  by  the  administration  of  nitroglycerine,  a  pill 
containing  one  grain  of  the  acetic  extract  of  colchicum  and 
three  grains  of  "  blue  pill "  should  be  given  at  night  and 
should  be  followed  by  a  dose  of  Epsom  salts  in  the  morning. 
When  the  administration  of  nitroglycerine  is  discontinued 
citrate  of  potassium  and  iodide  of  potassium  should  be 
given  for  some  time  thrice  a  day. 


Chap.  XIII.]  GOUTY    PHLEBITIS.  235 

Pseudo-ang-ina  pectoris. — For  the  treatment  of  this 
affection  a  dose  of  hot  brandy  and  water  should  be  given 
at  once,  and  a  mustard  leaf  should  be  applied  to  the  epigas- 
trium. On  the  subsidence  of  the  severe  symptoms  a  pill 
containing  one  grain  of  the  acetic  extract  of  colchicum  and 
three  grains  of  "  blue  pill "  should  be  given  at  night,  and 
should  be  followed  by  a  dose  of  Epsom  salts  in  the  morning. 

Gouty  phlebitis. — For  the  treatment  of  this  fairly 
common  form  of  irregular  gout  the  patient  sliould  be  kept 
in  the  recumbent  position,  and  any  sudden  movement  of 
the  affected  limb  must  be  prevented,  on  account  of  the 
danger  of  detaching  a  portion  of  thrombus  and  the  occur- 
rence of  consequent  embolism  of  the  pulmonary  artery. 
Equal  parts  of  glycerine  and  extract  of  belladonna  should 
be  smeared  over  the  affected  part,  arid  a  linseed  poultice 
with  some  of  tlie  glycerine  and  extract  of  belladonna  spread 
on  the  surface  should  be  applied  and  renewed  every  six 
hours.  In  addition  to  this  the  ordinary  treatment  of  the 
gouty  state  must  be  resorted  to. 

Gouty  sciatica. — For  the  treatment  of  this  painful 
affection  the  patient  must  be  kept  in  the  recumbent  posi- 
tion, and  in  severe  cases  the  pain  should  be  relieved  by  a 
hypodermic  injection  of  morphine.  Ammonium  chloride, 
given  in  doses  of  thirty  to  forty  grains  three  or  four  times 
a  day,  is  a  very  useful  drug  in  the  treatment  of  this  form  of 
irregular  gout.  Two  grains  of  salicylate  of  quinine  should 
also  be  given  in  a  pill  two  or  three  times  a  day.  These 
measures  should  be  supplemented  by  the  ordinary  treat- 
ment of  the  gouty  state. 

Gouty  neuritis. — Blistering  along  the  course  of  the 
affected  nerve-trunk  is  the  most  rapid  way  of  relieving  this 
painful  affection.  If  such  a  mode  of  treatment  should  not 
be  considered  desirable,  then  iodine  liniment  may  be  painted 
along  the  course  of  the  nerve-trunk,  and  hot  linseed  poultices 
applied  as  soon  as  the  iodine  is  dry,  and  kept  in  position 
by  a  bandage  loosely  applied.    Internally,  iodide  of  potassium 


236  GOUT:    TREATMENT.  [partiv. 

combined  with  small  doses  of  perchloride  of  mercury 
should  be  given. 

Insomnia  in  gouty  subjects. — Many  gouty  persons 
complain  of  insomnia  or  restlessness  when  in  bed.  This  is 
frequently  either  toxic  in  its  origin,  or  is  due  to  a  state  of 
high  tension  in  the  cerebral  arteries.  As  a  rule,  the  insomnia 
is  not  complete,  but  consists  of  restlessness,  interspersed 
with  varying  intervals  of  light  or  broken  slumber.  In  such 
cases,  careful  attention  should  be  given  to  the  state  of  the 
pulse,  the  heart,  and  the  condition  of  the  urine.  In  many 
cases  it  will  be  found  that  the  pulse  is  of  high  tension,  and 
is  associated  with  accentuation  of  the  aortic  second  sound, 
perhaps  reduplication  of  the  first  sound  in  the  vicinity  of 
the  apex  of  the  heart,  and  a  slight  degree  of  albuminuria. 
In  such  cases  the  insomnia  is  best  relieved  by  the  adminis- 
tration at  night  of  small  doses  of  "  blue  pill  "  or  calomel, 
combined  with  full  doses  of  the  extract  of  hyoscyamus. 
Bromide  of  ammonium  may  also  be  given  as  a  sedative, 
•and  as  a  drug  which  reduces  arterial  tension,  but,  with  such 
patients,  it  is  most  undesirable  to  resort  to  the  use  of  the 
ordinary  hypnotic  drugs. 

Irritable  temper. — For  the  treatment  of  the  irritable 
temper  of  gout.  Sir  Lauder  Brunton  recommends  the  admin- 
istration of  twenty  grains  of  bicarbonate  of  potassium  and 
ten  to  twenty  grains  of  bromide  of  potassium. 

Renal  calculi. — For  the  treatment  of  uric  acid  renal 
calculi  citrate  of  potassium  should  be  given  in  full  doses, 
so  as  to  produce  a  moderate  alkalinity  of  the  urine.  By  this 
means  the  further  deposition  of  free  uric  acid  in  the  kidneys 
is  prevented,  and  the  alkaline  urine,  moreover,  gradually 
carries  into  solution  the  uric  acid  already  deposited.  The 
free  drinking  of  ordinary  water  or  of  one  of  the  mineral 
waters  of  the  simple  kind  should  be  advised. 

Gouty  eczema. — Of  the  purely  internal  causes  of 
eczema,  disorder  of  the  gastro-intestinal  tract  should,  in 
my  opinion,  be  placed  first.     The  gouty  person  is  one  who 


Chap.  XIII.]  GOUTY    ECZEMA.  237 

is  not  only  liable  to  such  disorder  and  to  faulty  assimilation 
of  food,  but  is  also  particularly  vulnerable  to  inflammations 
of  the  synovial  and  mucous  membranes,  and  of  the  skin. 

In  the  treatment  of  this  form  of  irregular  gout  special 
attention  should  be  given  to  two  details.  One  is  to  see 
that  the  bowels  are  freely  opened,  which  at  the  outset  may 
be  secured  by  the  administration  of  "  blue  pill  "  or  calomel 
followed  by  a  saline  ;  the  other  point  is  that  entire  abstention 
from  alcohol  is  most  desirable,  at  all  events  during  the 
treatment  and  persistence  of  the  eczema.  It  is  best  that 
any  form  of  alcohol  should  be  abstained  from,  but  the  pro- 
hibition applies  more  especially,  in  my  experience,  to  the 
red  wines.  I  have  met  with  several  cases  occurring  among 
gouty  individuals  past  the  middle  age  of  life  in  whom 
two  or  three  glasses  of  claret  or  burgundy  will  in  the  course 
of  a  few  hours  cause  the  development  of  an  eczema.  During 
the  irritative  stage  of  dry  gouty  eczema  I  have  found  the 
application  of  a  lotion  consisting  of  liquor  plumbi  sub- 
acetatis  5J,  liquor  carbonis  detergens  5J,  aqua  sambuci  ad 
Oj,  most  soothing,  especially  if  followed  by  the  use  of  a 
simple  dusting-powder,  such  as  cimolite  powder.  For 
the  acute  moist  type  of  eczema  a  similar  lotion,  but  with 
a  preparation  of  opium  replacing  the  tar-solution,  is 
advisable. 

When  the  eczema  is  in  a  chronic  condition  much  benefit 
is  usually  experienced  from  immersion  in  sulphur-baths, 
such  as  those  of  Harrogate,  Strathpeffer,  Aix-les-Bains, 
etc.  After  the  bath  the  skin  should  be  carefully  dried. 
and  a  dusting-powder  such  as  cimolite  powder  freely  applied. 
In  cases  of  gouty  eczema  and  gouty  pruritus  a  careful 
dietary  must  be  enforced,  care  being  taken  to  forbid  all 
articles  which  the  experience  of  the  patient  in  the  past 
has  shown  to  produce  dyspepsia.  Persons  who  are  subject 
to  attacks  of  gouty  eczema  should  avoid  such  acid  fruits 
as  strawberries,  gooseberries,  apples  and  pineapples ; 
rhubarb   also   should   be   excluded   from   the   dietary.     As 


238  GOUT:    TREATMENT.  [part  iv. 

regards  the  medicinal  treatment  of  gouty  eczema,  my 
experience  is  that  it  is  not  necessary  to  give  the  ordinary 
anti-gout  remedies,  such  as  colchicum,  etc.  It  is  much 
more  important  to  treat  the  dyspepsia  and  the  catarrhal 
condition  of  the  gastro-intestinal  tract,  which  are  generally 
present  as  associated  or  causative  conditions,  by  the  admin- 
istration of  subcarbonate  of  bismuth  with  the  bicarbonate 
of  sodium  or  the  bicarbonate  of  potassium. 

In  cases  of  gouty  pruritus,  or,  as  it  is  sometimes  termed, 
latent  gouty  eczema,  the  severe  itching  is  frequently  relieved 
by  the  use  of  carbolic-acid  lotion,  or  the  itching  attending 
pruritus  and  urticaria  may  be  relieved  by  the  application 
of  the  following  lotion  : — 

Liq.   Plumbi  Subacet.  .  .  .  .      5ij- 

Tinct.   Opii  ......      5iv. 

Aq.   Rosae  ad       .....  .      ^viij. 

Rubbing  the  skin  with  a  menthol  cone  moistened  with 
water  is  frequently  useful  in  relieving  the  irritation.  For 
the  treatment  of  dry  skin  eruptions  Sir  William  Roberts 
recommends  the  skin  to  be  rubbed  with  a  piece  of  smooth 
hard  paraffin  night  and  morning,  so  as  to  leave  on  the 
skin  a  delicate  coating,  which  then  probably  acts  by  pro- 
tecting the  cutaneous  surface  from  the  air. 

Treatment  of  g-outy  grlycosuria  and  gouty  diabetes. 
— Dietetic  treatment. — Careful  dietetic  treatment  should 
be  resorted  to,  without,  however,  restricting  the  diet  too 
much.  An  excessively  nitrogenous  diet  is  to  be  avoided 
as  tending  to  accentuate  the  gouty  condition,  but  no  hard 
and  fast  rules  as  to  the  amount  of  diet  can  be  laid  down. 
Each  case  must  be  treated  by  ascertaining  what  amount 
of  proteids,  fats,  and  carbohydrates  is  best  borne  by  the 
individual.  Toasted  bread,  milk,  and  milk  puddings  made 
with  rice,  sago,  and  tapioca  are  generally  permissible  in 
this  form  of  glycosuria.  The  best  test  of  the  suitability 
of  the  diet  is  the  fact  that  the  weight  of  the  patient  is  not 
diminishing,  while,  at  the  same  time,  the  excretion  of  sugar 


CHAP.xiii]  RETROCEDENT    GOUT.  239 

is  becoming  less.  The  patient  should,  therefore,  be  weighed 
once  a  week,  and  the  whole  of  the  urine  for  twenty-four 
hours  should  be  collected  once  a  week,  measured,  and  the 
quantity  of  sugar  determined  in  a  sample  of  the  mixed 
urines,  so  that  the  total  output  of  sugar  for  the  twenty- 
four  hours  may  be  known. 

Medicinal  treatment. — A  pill  containing  one  grain  of 
"  blue  pill,"  one  grain  of  acetic  extract  of  colchicum,  and 
two  grains  of  euonymin  should  be  given  every  other  night. 
A  mixture  containing  thirty  grains  of  ammonium  chloride 
and  fifteen  minims  of  dilute  nitro-hydrochloric  acid  in 
each  dose  should  be  taken  three  times  a  day  ;  this  mixture 
acts  as  a  stimulant  to  hepatic  metabolism.  Opium  and 
its  alkaloids  are  best  avoided.  A  list  of  the  mineral 
waters  best  suited  for  the  treatment  of  gouty  glycosuria 
and  gouty  diabetes  is  given  later  on. 

Treatment  of  retrocedent  or  metastatic  g-out. — 
Immediate  treatment. — If  the  symptoms  are  urgent  some 
brandy  should  be  immediately  given,  and,  if  necessary,  a 
hypodermic  injection  of  morphine  should  be  administered, 
provided  marked  albuminuria  does  not  exist.  If  the 
metastatic  seizure  is  a  severe  one,  and  especially  if  it  affects 
either  the  heart  or  brain,  it  may  be  desirable  to  reinduce  an 
attack  of  articular  gout  by  placing  the  feet  in  a  hot  mustard- 
and-water  bath,  containing  a  full  tablespoonful  of  flour 
of  mustard  to  a  gallon  of  water. 

Treatment  of  the  gastro-intestinal  form. — A  mustard 
leaf  should  be  applied  to  the  epigastrium,  and  a  mixture 
containing  bismuth  subcarbonate,  sodium  bicarbonate, 
and  hydrocyanic  acid  should  be  given.  If  there  is  much 
depression  suitable  stimulants  must  be  employed. 

Treatment  of  the  cardiac  form. — Heart  tonics,  such  as 
digitalis,  convallaria,  or  strophanthus,  and  brandy,  should 
be  administered.  A  mustard  leaf  may  be  applied  to  the 
epigastrium.  If  an  anginal  attack  occurs,  then,  in  addition 
to  this  treatment,  a  dose  of  nitroglycerine  should  be  given 


240  GOUT:    TREATMENT.  [Partiv. 

at  once,  or  an  inhalation  of  nitrite  of  amyl  employed,  and, 
if  necessary,  a  mustard  leaf  should  be  placed  over  the 
prsecordial  region.  For  the  treatment  of  syncopal  attacks 
the  patient  should  be  immediately  placed  in  the  recumbent 
position,  with  the  foot  of  the  sofa  or  bed  raised  ;  some  hot 
brandy  and  water  should  be  given,  warmth  and  friction 
applied  to  the  extremities,  and  a  mustard  leaf  placed  over 
the  epigastrium. 

Treatment  of  the  cerebral  form. — If  the  patient  is  plethoric, 
and  if  the  pulse  is  hard,  and  stupor  or  coma  supervenes, 
venesection  should  be  performed,  and  from  eight  to  sixteen 
ounces  of  blood  withdrawn  ;  in  less  urgent  cases  six  leeches 
may  be  applied  to  the  mastoid  region.  Five  grains  of 
calomel  should  afterwards  be  administered  by  the  mouth, 
and  a  turpentine  enema  given. 


CHAPTER    XIV. 

DIET   IN   GOUT. 

General  principles  of  dieting — Digestibility  of  food — Chittenden's 
views — Animal  food — Purin  -  free  diet — Vegetable  food — 
Starchy  and  saccharine  foods — Fruits — Beverages — Simplicity 
of  meals  —  The  Salisbury  diet  —  Plan  of  diet  for  gouty 
subjects. 

General  principles  of  dieting*.  —  No  hard-and-fast  lines 
as  to  dietary  can  be  laid  down  in  the  treatment  of 
gout.  Each  individual  must  be  carefully  considered  as 
regards  his  habit  of  body,  his  capacity  for  the  digestion  of 
different  articles  of  food,  the  amount  of  exercise  he  is  able 
to  take,  and  the  nature  of  his  work.  Derangements  of 
the  gastro-intestinal  tract  constitute  a  most  important 
factor  in  the  development  of  acute,  chronic  and  irregular 
gout  ;  in  all  forms  of  gout,  whether  regular  or  irregular, 
there  is  one  invariable  symptom,  viz.,  digestive  disturbance. 
It  is,  therefore,  of  the  utmost  importance  to  secure  and 
maintain  a  healthy  condition  of  the  gastro-intestinal 
mucous  membrane,  and  a  normal  daily  evacuation,  in 
order  to  guard  against  auto-intoxication,  which  is  un- 
doubtedly an  early  factor  in  the  development  of  the  gouty 
condition.  The  individual  who  is  subject  to  gouty  attacks 
can  certainly  diminish  the  number  and  severity  of  the 
attacks,  and  in  many  cases  can  prevent  their  recurrence, 
by  careful  attention  to  diet,  to  the  quality  and  the  quantity 
of  fluid  taken,  to  exercise,  and  to  a  sufficient  daily  action 
of  the  bowels. 

Gouty    people    may   for    the    purposes    of    the    con- 
sideration of   diet  be  roughly  grouped  into   three  classes  i 
e  24L 


242  GOUT:    TREATMENT.  [Partiv. 

(i)  those  who  suffer  from  more  or  less  frequent  attacks 
of  acute  gout  ;  (2)  those  who  have  never  suffered  from  an 
acute  attack,  but  who  are  constantly  subject  to  some  chronic 
form  of  regular  or  irregular  gout,  especially  after  slight 
indiscretion  in  diet  ;  and  (3)  those  who  are  only  affected 
with  gouty  symptoms  (generally  of  the  irregular  kind) 
when  they  eat  or  drink  certain  articles,  and  who  therefore 
in  order  to  avoid  these  gouty  symptoms  have  to  be  specially 
watchful  over  their  diet.  As  Mouillot  has  observed,  it 
will  usually  be  found  that  patients  in  classes  2  and  3  are 
the  offspring  of  those  who  have  suffered  from  acute  gout. 

In  advising  as  to  the  diet  of  any  particular  gouty  in- 
dividual the  personal  factor  is  a  most  important  one  to 
consider,  and  it  is  wise  to  gain  some  knowledge  as  to  the 
likes  and  dislikes  of  the  individual  with  regard  to  food. 
In  this  connection  it  is  well  to  remember  the  saying  of 
Sydenham,  that  "  more  importance  is  to  be  attached  to 
the  desires  and  feelings  of  the  patient,  provided  they  are 
not  excessive,  than  to  doubtful  and  fallacious  rules  of 
medical  art." 

It  is  well  known  that  the  excessive  consumption  of  rich 
nitrogenous  food,  combined  with  excesses  in  wine  and 
malt  liquors,  both  induces  and  excites  gout.  The  com- 
parative immunity  of  females  and  young  people  from  gout 
is  mainly  explained  by  the  absence  of  such  determining 
causes  of  the  gouty  attack,  combined,  in  the  case  of  young 
people,  with  the  absence  of  predisposing  cause,  and  also 
with  the  fact  that  the  secreting  functions  are  in  full  activity. 
The  subjects  of  gout  are  generally  persons  who  live  well 
and  consume  a  large  amount  of  animal  food.  Budd,  speak- 
ing from  a  long  and  extensive  professional  connection  with 
a  large  rural  district,  states  that  he  never  knew  an  instance 
of  gout  occurring  in  an  agricultural  labourer. 

Dig'estibility  of  food. — Gout,  which  is  a  toxaemia 
originating  to  a  great  extent  in  the  alimentary  tract,  derives 
its  toxic  products  from  the  improper  digestion  of  food-stuffs. 


Chap.  XIV.]  DIET.  243 

Whatever  articles  of  food  can  be  properly  digested  by  the 
gouty  are  therefore  suitable  articles  for  their  dietary. 
The  physical  condition  of  an  article  of  food  to  a  very 
great  extent  determines  its  digestibility.  By  digestibility 
is  meant  not  necessarily  the  extent  to  which  it  is  absorbed 
into  the  blood,  but  the  power  of  disposing  of  the  food  by 
the  stomach,  without  the  production  of  discomfort  or  pain. 
The  digestibility  of  the  various  kinds  of  fish,  and  of  the 
flesh  of  birds  and  animals,  depends  on  the  length  of  the 
muscular  fibres,  and  on  the  amount  of  fat  deposited  between 
the  fibres.  The  shorter  the  fibres,  and  the  smaller  the  amount 
of  fat  deposited  between  them,  the  more  digestible  will 
the  article  of  food  be.  If  an  article  of  food  tends  to  be 
swallowed  in  a  solid  lump,  such  for  instance  as  new  bread 
or  new  potatoes,  so  as  to  prevent  the  ready  permeation 
of  the  substance  by  the  digestive  juices,  it  tends  to  be 
indigestible  purely  by  virtue  of  its  physical  condition. 
If  such  articles  were  first  reduced  to  minute  subdivision  by 
thorough  mastication  and  insalivation,  their  indigestibility, 
as  far  as  ordinary  individuals  are  concerned,  would  dis- 
appear. 

It  is  not  so  much  a  matter  of  importance  to  know 
whether  or  not  any  particular  article  of  food  contains  uric 
acid  or  its  antecedents,  as  to  know  what  are  its  proper- 
ties as  regards  digestibility  and  as  regards  its  influence  on 
the  processes  which  are  concerned  in  the  conversion  of 
food-stuffs  into  body-stuffs.  The  researches  of  Pawlow 
have  shown  that  the  food  value  of  any  particular  article 
of  diet  must  depend  to  a  large  extent  upon  the  amount  of 
energy  necessary  for  its  digestion. 

If  gouty  persons  partake  of  meals  of  too  complex  a 
character,  then,  owing  to  the  abnormal  intestinal  and  hepatic 
metabolism  of  such  subjects,  excessive  production  and  im- 
perfect elimination  of  toxic  products  may  result.  Although 
both  excessive  production  and  imperfect  elimination  of 
these    abnormal    products   of    digestion    go    more    or    less 


244  GOUT:    TREATMENT.  [pahtiv. 

together,  yet  it  is  a  matter  of  fairly  frequent  observation 
that  some  gouty  persons  seem  to  be  especially  the  victims 
of  excessive  production  of  toxic  products,  and  others  to 
be  mainly  affected  by  defective  elimination. 

In  regulating  diet  it  is  very  important  to  bear  in  mind 
that  it  is  in  many  cases  not  advisable  to  change  too  suddenly 
the  diet  to  which  the  patient  is  accustomed.  The  com- 
position of  the  various  digestive  secretions  is  adapted  to 
the  food  they  have  to  digest,  so  that  the  individual  who 
habitually  eats  an  excess  of  proteid  comes  in  time  to  have 
gastric  and  pancreatic  secretions  which  will  digest  proteid 
well,  and  if  the  carbohydrates  of  the  food  have  been  limited 
he  will  also  have  a  limited  capacity  for  their  digestion  ;  so 
that  if  a  sudden  change  of  diet  is  ordered,  it  takes  a  little 
time  for  the  constituents  of  the  digestive  secretions  to 
adapt  themselves  to  the  altered  food,  and  in  the  meantime 
the  patient  may  feel  worse  for  the  change  of  diet  which 
will  ultimately  benefit  him.  The  diet  suitable  to  any 
patient  will  depend  on  the  digestive  capability  of  that 
patient,  and  should  be  regulated  accordingly ;  it  is  important 
to  remember  to  treat  the  individual  as  well  as  the  disease. 

Maintenance  of  a  healthy  alimentary  tract. — 
If,  as  is  probably  the  case,  the  toxin  or  toxins  of  gout  are 
produced  in  the  intestinal  tract,  it  is  obvious  that  the  first 
efforts  at  treatment  should  be  directed  to  obtaining  a 
healthy  alimentary  tract,  and  to  modifying  those  habits  of 
living  which  have  caused  gastro-intestinal  derangement. 

Before  deciding  how  these  objects  can  be  attained,  it  is 
first  necessary  shortly  to  consider  some  points  in  the  diges- 
tive processes  which  take  place  in  the  small  intestine. 
Under  normal  conditions  bacterial  decomposition  does  not 
take  place  in  the  upper  part  of  the  small  intestine,  as  the 
duodenum  and  upper  portion  of  the  jejunum  are  practically 
sterile.  The  conditions  which  favour  increased  bacterial 
growth  in  the  intestine  are  (i)  increase  in  the  amount  of 
proteid  food  (the  number  of  bacteria  in  the  intestine  varying 


Chap.  XIV.]  DIET.  245 

directly  with  tlae  amount  of  proteid  food),  and  (2)  the  reaction 
of  the  intestinal  contents.  As  long  as  the  contents  are 
acid,  bacterial  growth  is  inhibited,  but  when,  owing  to 
gastric  or  intestinal  dyspepsia,  the  intestinal  secretion  is 
changed,  the  reaction  of  the  intestinal  contents  changes, 
and  great  increase  in  the  number  of  intestinal  bacteria 
takes  place,  while  at  the  same  time  their  pathogenicity  is 
increased.  Therefore,  the  growth  of  bacteria  in  the  intestinal 
tract  and  their  pathogenicity  will  vary  directly  with  the 
amount  of  proteid  food  and  the  amount  of  catarrh 
present. 

These  facts  obviously  have  a  great  bearing  on  the  treat- 
ment of  gout,  and  explain  how  it  is  that  excess  of  proteid 
food,  and  those  forms  of  alcohol  which  tend  to  produce 
intestinal  catarrh,  have  such  a  strong  influence  on  the 
production  of  gout. 

As  regards  the  amounts  of  proteid,  fat,  and  carbo- 
hydrate that  the  ordinary  individual  of  average  body  weight 
needs  during  the  twenty-four  hours  to  satisfy  the  normal 
nutritive  requirements  of  the  body,  it  may  be  answered 
in  a  general  way  that  he  requires  enough  of  these  foodstuffs 
to  establish  physiological  and  nitrogenous  equilibrium,  suffi- 
cient, that  is,  to  keep  up  the  strength  of  body  and  mind  that 
is  essential  to  good  health,  to  maintain  the  highest  degree 
of  physical  and  mental  activity  with  the  smallest  amount 
of  friction  and  the  least  expenditure  of  energy,  and  to  pre- 
serve and  heighten  if  possible  the  ordinary  resistance  of 
the  body  to  disease  germs.  Chittenden's  opinion  is  that 
the  smallest  amount  of  food  that  will  accomplish  these 
ends  is  the  ideal  diet.  There  must  be  enough  to  supply 
the  true  needs  of  the  body,  but  any  great  surplus  over  and 
above  what  is  really  called  for  may  in  the  long  run  prove 
an  undesirable  addition.  It  is  therefore  necessary  to  have 
definite  and  precise  knowledge  of  the  amount  of  proteid, 
and  of  the  total  calorific  value,  needed  to  maintain  the 
body   in   the  highest  state  of    ef&ciency,  before  any  very 


246  GOUT:    TREATMENT.  [partiv. 

exact  estimate  of  what  constitutes  over-nutrition  or  under- 
nutrition can  be  formed. 

It  must  be  understood  that  no  diet  contains  an  adequate 
amount  of  proteid  food  that  does  not  keep  up  a  condition 
of  nitrogenous  equihbrium.  If  the  nitrogen  output  per- 
sistently exceeds  the  nitrogen  intake,  it  is  obvious  that 
the  body  is  feeding  on  its  own  tissue,  which  means  that  the 
proteid  of  the  food  is  insufficient  in  amount.  On  the  other 
hand,  a  diet  that  suffices  to  maintain  body  weight,  with 
estabhshment  of  nitrogen  equilibrium,  should,  so  far  as  our 
present  knowledge  goes,  be  quite  adequate  to  meet  all  the 
wants  of  the  body  for  proteid  matter. 

Chittenden  considers  that  the  daily  consumption  of 
proteid  food  far  beyond  the  amount  required  to  maintain 
health,  strength,  mental  and  physical  vigour,  body  weight, 
and  nitrogen  equilibrium,  constitutes  a  form  of  over-nutrition 
as  serious  in  its  menace  to  the  health  and  welfare  of-  the 
human  race  as  many  other  evils  more  striking  in  character. 
He  believes  that  there  are  more  people  suffering  to-day 
from  over-eatmg  and  over-nutrition  than  from  the  effects 
of  alcoholic  drink.  He  maintains  that  if  people,  as  shown 
by  experiments,  can  maintain  nitrogen  equilibrium  and 
body  weight,  gain  in  strength,  show  greater  freedom 
from  muscular  fatigue,  lose  their  rheumatic  and  gouty 
symptoms,  regain  a  smooth  and  soft  skin,  exhibit  greater 
freedom  from  colds,  retain  the  normal  haemoglobin  content 
of  their  blood,  and  in  every  recognisable  way  manifest  a 
good  condition  of  health  on  a  low  proteid  diet,  there  should 
be  no  hesitation  in  accepting  the  teaching  which  the  scientific 
data  point  to.  Chittenden's  experiments  show  that  it  is 
quite  possible  to  maintain  body  weight,  and  keep  up  nitrogen 
equilibrium,  and  preserve  strength,  vigour,  and  good 
health  on  from  34  grammes  to  56  grammes  of  proteid 
matter  per  day.  My  own  experience  is  that,  on  a  diet 
containing  this  amount  of  proteid,  gouty  persons  maintain 
their  nitrogen  equilibrium  and  body  weight,  become  free 


Chap.  XIV.]  DIET.  247 

from  most  of  their  gouty  symptoms,  and  generally  enjoy 
a  good  condition  of  health. 

Animal  food. — As  regards  the  question  of  meat,  it 
must  be  remembered  on  the  one  hand  that  animal  foods 
constitute  to  the  majority  of  people  the  most  attractive 
and  appetising  forms  of  diet,  and  are  therefore  likely  to  be 
taken  in  excess  ;  hence  the  necessity  for  limiting  the  amount 
to  be  taken.  But,  on  the  other  hand,  it  must  be  borne  in 
mind  that  it  is  most  desirable  to  increase  the  combustion 
and  the  oxidative  powers  within  the  tissues.  In  my  opinion 
it  is  absolutely  erroneous  to  exclude  from  the  dietary  of 
the  gouty  such  articles  as  meat,  fish,  and  tea,  because  they 
are  assumed  to  contain  uric  acid. 

The  so-called  estimations  of  uric  acid  in  those  articles 
of  diet  are  not,  as  I  have  elsewhere  pointed  out,  estimations 
of  uric  acid  at  all.  Moreover,  the  deduction  is  an  erroneous 
one  that  because  uric  acid  is  a  nitrogenous  body,  it  must 
therefore  be  directly  derived  from  nitrogenous  constituents 
of  the  food,  the  consumption  of  which  must  consequently 
be  avoided. 

The  contention  that  a  meat  diet  is  poisonous  to  the 
human  body,  on  account  of  the  uric  acid  that  it  contains, 
or  produces,  is  preposterous,  in  view  of  the  facts  that  many 
races  have  maintained  robust  health  on  such  a  diet,  and 
that,  for  centuries,  the  beef-eating  Englishmen  have  man- 
aged to  spread  and  advance  knowledge  and  civilisation, 
and  to  acquire  territory  in  all  parts  of  the  world.  Surely, 
if  meat  is  the  poison  which  a  certain  class  of  enthusiasts 
and  fanatics  maintains  it  to  be,  we  as  a  nation  should  have 
ceased  to  exist  long  ere  this.  Harry  Campbeh,  in  his 
interesting  series  of  articles  on  "  The  Evolution  of  Man's 
Diet,"  has  shown  that  man  has  evolved  from  the  ape  on 
a  highly  animalised  diet,  and  that  it  was  on  such  a  diet 
that  the  intehectual  faculties,  and  the  faculty  of  language, 
which  distinguish  him  from  the  beast,  were  developed. 
It  is  interesting  to  note  that  the  recent  remarkable  advance 


248  GOUT:    TREATMENT.  [^ARxrv. 

of  the  Japanese  to  the  position  of  a  first-class  Power  amongst 
the  nations  is  concurrent  with  the  adoption  of  a  more  animal- 
ised  diet  by  them.  The  fact  that  many  races  in  the  past 
have  been  largely  carnivorous  as  regards  their  diet,  and 
that  some  are  so  even  at  the  present  time  (Esquimaux, 
Andamanese,  etc.),  shows  that  the  assumption  that  animal 
foods  are  necessarily  poisonous  to  man  is  an  entirely  erroneous 
one..  No  class  of  food-stuff  gives  so  great  an  amount  of 
energy  and  produces  so  much  heat  as  animal  food,  and 
none  is  more  easily  digested  by  the  majority  of  gouty 
people.  On  the  other  hand,  the  tendency  with  most  people 
in  this  country,  as  I  shall  have  occasion  to  remark  later  on, 
is  to  eat  too  much,  and  to  masticate  too  little,  and  this 
applies  to  the  consumption  not  only  of  meat  but  of  all 
other  solid  articles  of  diet. 

On  the  whole,  it  may  be  stated  that  animal  food,  such 
as  fish,  chicken,  game  and  meat,  is  best  suited  to  the  majority 
of  gouty  cases,  whilst  foods  of  the  farinaceous  class  are  most 
likely  to  disagree.  White  meats,  such  as  chicken  and  fish, 
are  more  digestible  than  red  meats.  The  quantity  of 
meat,  and  especially  of  red  meat,  must  be  restricted  in 
those  cases  in  which  the  kidneys  are  imperfectly  performing 
their  eliminating  functions,  as  evidenced  by  a  pale  urine, 
of  low  specific  gravity,  and  deficient  in  urea  and  purin- 
bases. 

Pupln-free  diet. — A  purin-free  diet  is  one  selected 
from  milk,  cheese,  butter,  white  bread,  cereal  foods,  nuts, 
and  fruit.  Milk  suits  gouty  people  very  well,  and  milk 
has  a  special  effect  in  reducing  the  number  of  intestinal 
bacteria,  their  number  being  less  with  a  milk  diet  than 
with  any  other. 

It  is  true  that  a  purin-free  diet  has  proved  of  benefit 
in  certain  cases  of  disease,  but  there  is  every  reason  to 
believe  that  in  such  cases  an  equal  benefit  would  be  obtained 
by  a  mixed  diet,  in  which  the  proteid  consumption  is  kept 
down  to  a  minimum.     So  long  as  temperance  in  the  ingestion 


tHAP.  XIV.]  DIET.  249 

of  proteid  is  observed,  it  matters  but  little  from  what  source 
the  proteid  is  derived. 

From  Walker  Hall's  experiments  it  would  appear 
reasonable  to  administer  sweetbread  to  gouty  patients, 
since  its  nuclein  portion  is  only  slightly  absorbed,  for 
thymus  sweetbread  contains  principally  adenin,  which  is 
rapidly  excreted,  and  pancreas  sweetbread  contains  mainly 
guanin,  an  amino-purin  incapable  of  increasing  the  urinary 
purin  output  and  of  exerting  any  injurious  effects  upon  the 
tissues. 

Vegetable  food. — A  fair  proportion  of  vegetable  food 
should  be  taken  with  two  meals  each  day.  The  choice  of 
vegetables  will  depend  upon  the  digestive  capacity  of  the 
patient  ;  but,  excepting  the  potato,  as  a  rule  those  vegetables 
that  grow  above  ground  are  preferable  to  root  vegetables. 
Whereas  the  mineral  constituents  of  meat  exercise  a  marked 
effect  in  diminishing  the  solubility  of  a  gouty  deposit,  the 
mineral  constituents  of  most  vegetables  exercise  a  marked 
power  in  increasing  its  solubility.  The  vegetables,  the 
mineral  constituents  of  which  I  find  are  most  efficacious 
in  this  respect,  are  spinach,  Brussels  sprouts,  potatoes, 
cabbage,  and  French  beans.  At  the  same  time,  it  must 
be  borne  in  mind  that  with  certain  patients  some  of  these 
vegetables  may  tend  to  produce  some  form  of  dyspepsia  ; 
and  I  must  again  insist  that  in  the  dieting  of  the 
gouty  no  hard-and-fast  rules  can  be  laid  down,  but  the 
idiosyncrasy  of  each  patient  to  various  articles  of  diet 
must  be  made  the  subject  of  careful  observation  and  study. 
Due  consideration  should  also  be  given  to  the  patient's 
experience  of  what  articles  of  diet  disagree  or  agree  with 
him. 

Starchy  and  saccharine  foods. — A  diet  that  too 
largely  consists  of  bread  and  starchy  material  Jeads  to 
gravel  in  a  number  of  cases.  The  frequency  of  uric  acid 
gravel  and  stone  among  the  rice-fed  Hindoos  is  well  known. 

Starchy  articles  of  food  should  be  especially  limited  in 


250  GOUT:    TREATMENT.  (partIV, 

amount  in  those  gouty  individuals  who  are  subject  to  gastric 
hyperacidity  (hyperchlorhydria).  This  condition  is  not 
due  to  gastric  fermentation,  but  to  an  excessive  secretion 
of  hydrochloric  acid  by  the  gastric  glands,  and  is  a  common 
cause  of  dyspepsia,  and  ultimately  of  gastric  dilatation. 
It  is  due  to  an  acid  dyscrasia,  as  the  result  of  which  the 
secretion  of  gastric  juice  does  not  cease  with  the  digestion 
of  the  proteid  materials  of  the  food,  but  continues  after 
they  have  been  disposed  of.  The  result  is  that  a  considerable 
portion  of  the  starchy  materials  is  kept  back  in  the  stomach, 
and  this  retained  starch  keeps  up  the  gastric  secretion, 
without  at  the  same  time  giving  it  any  work  to  do. 

When  intestinal  fermentation  and  putrefaction  occur, 
as  evidenced  by  a  sense  of  discomfort  after  a  meal,  I  attach 
great  importance  to  the  reduction  of  the  starchy  articles 
of  food,  but  not  to  the  total  exclusion  of  what  I  believe 
to  be  comparatively  harmless,  the  potato.  It  is  remarkable 
how  frequently  one  hears  from  gouty  patients  the  emphatic 
statement,  "  I  never  eat  potatoes."  I  must  confess  that 
I  do  not  know  of  any  good  and  sufficient  reason  for  a 
wholesale  condemnation  of  this  common  article  of  diet. 
Undoubtedly  amongst  those  gouty  patients  who  suffer  from 
an  inability  to  digest  starchy  articles  of  diet — in  other 
words,  who  suffer  from  amylaceous  dyspepsia — a  reduction 
for  the  time  in  the  amount  of  starchy  foods  taken,  including 
potatoes,  is  desirable  ;  but  the  recognition  of  the  existence 
of  amylaceous  dyspepsia  is  a  fairly  easy  matter,  and  when 
present  it  can  be  suitably  treated.  Certainly  those  who  are 
gouty  and  fat  should  be  very  sparing  in  the  use  of  potatoes, 
as  of  other  carbohydrate  forms  of  food.  I  wish,  however, 
to  protest  against  the  too  general  exclusion  from  the  food 
of  the  gouty  of  so  popular  and  useful  an  article  of  diet  as 
the  potato.  The  best  form  in  which  potatoes  can  be  taken 
by  the  gouty  is  the  crisp  form,  which  requires  thorough 
mastication  and  insalivation.  Boiled  new  potatoes  should 
be  absolutely  interdicted  to  the  gouty. 


Chap.  XIV.]  DIET.  251 

Equally  wrong,  in  my  opinion,  is  the  total  exclusion  of 
sugar  from  the  dietary  of  all  gouty  individuals.  Undoubtedly 
in  certain  individuals  sugar  may  do  harm,  as  in  the  cases  of 
gouty  persons  who  are  fat,  or  who  suffer  from  glycosuria,  or 
who  are  prone  to  attacks  of  eczema  ;  and  in  such  it  should 
be  cut  off ;  but  that  is  no  reason  for  the  exclusion  of  it 
from  the  dietary  of  all  gouty  patients.  I  know  of  many 
gouty  individuals  who  take  sugar  with  absolute  impunity. 
Some  gouty  subjects  undoubtedly  digest  very  badly  all 
starchy  articles  of  diet,  and  in  such  fats  may  well  take  the 
place  of  starches.  Fat  bacon,  properly  cooked,  is  generally 
well  digested  by  gouty  individuals. 

Subjects  who  are  both  gouty  and  fat  should  avoid 
sugar,  but  undoubtedly  sugar  may  be  taken  with  advantage 
by  those  who  are  gouty  and  thin,  and  such  subjects  may 
also  take  in  moderation  marmalade  and  wholesome  jams. 
Bread  may  advantageously  be  given  as  crisp  toast,  or  in 
the  form  of  rusks,  or  in  the  "  Zwieback  "  or  twice-baked 
form,  as  in  these  conditions  it  requires  thorough  mastication 
and  insalivation. 

In  those  cases  in  which  it  is  desirable  to  reduce  the 
carbohydrate  intake,  such  restriction  may  be  achieved 
(i)  by  cutting  off  sugar,  and  all  articles  containing  any  form 
of  sugar  ;  (2)  by  carefully  graduating  (by  weight)  the  daily 
intake  of  starch-containing  foods,  so  as  to  attain  the 
minimum  consistent  with  adequate  nutrition  in  each 
individual  case  ;  (3)  by  similarly  graduating  the  intake  of 
fats  if  necessary  ;  and  (4)  by  throwing  the  onus  of  nutrition 
to  a  considerably  greater  extent  than  previously  upon  fish, 
lean  meat,  green  non-starchy  vegetables,  and  gelatinous 
soups. 

Fruits. — Any  fruit  which  from  experience  is  known  to 
agree  with  the  individual  may  be  taken  by  gouty  subjects. 
Apples  and  oranges  generally  agree  best.  Uncooked  fruit 
should  never  be  taken  at  a  meat  meal,  and  is  best  consumed 
fasting  fairly  early  in  the  day,  as  between  breakfast  and  lunch. 


252  GOUT:    TREATMENT.  [p^rtiv. 

It  should  always  be  thoroughly  masticated.  Strawberries 
are  frequently  avoided  by  the  gouty  owing  to  their  pro- 
ducing in  some  subjects  a  certain  amount  of  temporary 
irritation  of  the  skin,  but  such  irritation  generally  passes 
off  in  a  short  time.  In  a  few  subjects  strawberries  produce 
eczema  or  some  other  rash,  but  such  cases  merely  represent 
idiosyncrasy  to  the  special  fruit,  and  necessarily  such 
individuals,  whether  gouty  or  not,  should  not  eat  straw- 
berries. I  am,  however,  strongly  of  opinion  that  the 
indiscriminate  banishment  of  strawberries  from  the  dietary 
of  the  gouty  is  unnecessary.  Except  in  those  cases  in 
which  there  is  an  idiosyncrasy  to  their  use  they  constitute 
a  good  article  of  diet  for  the  gouty,  on  account  of  their 
delicious  flavour,  their  antiscorbutic  properties,  and 
their  richness  in  potassium  salts.  It  is,  however,  very 
necessary  that  they  should  be  ripe  and  fresh.  They  are 
soon  prone  to  decomposition,  and  in  such  a  state  they  aid 
in  the  development  of  those  intestinal  fermentations  which 
are  so  inimical  to  the  gouty. 

Beverag"es. — It  is  my  custom  to  question  closely  each 
gouty  patient  that  I  see,  not  only  as  to  the  nature  of  the 
beverages  taken,  but  also  as  to  their  amount ;  and  my 
general  experience  is  that  the  great  majority  of  people 
suffering  from  gout  take  an  insufficient  quantity  of  water 
to  drink.  Consequently  there  is  an  inadequate  flushing  of 
the  liver,  kidneys,  and  other  organs  and  tissues,  and  there- 
fore imperfect  removal  of  waste  and  toxic  products.  More 
especially  does  one  find  this  insufficient  consumption  of 
fluid  among  female  patients,  in  many  cases  due  to  the 
absurd  and  erroneous  belief  that  a  diminution  in  the  amount 
of  fluid  taken  tends  to  keep  down  the  body-weight  and  to 
prevent  the  occurrence  of  obesity.  Taking  from  my  case- 
books ten  consecutive  cases  of  gout  occurring  in  ladies 
whom  I  carefully  questioned  as  to  the  amount  of  fluid  con- 
sumed per  diem,  I  find  that  amongst  these  ten  the  amount 
averaged   only   26   fluid   ounces  ;     this   included   all  fluid, 


Chap.  XIV.]  DIET.  253 

whether  taken  as  water,  tea,  coffee,  soup,  wine,  ale,  etc. 
The  amount  is  obviously  insufficient  for  the  proper  flushing 
of  the  system.  For  the  treatment,  as  well  as  for  the  pre- 
vention, of  the  gouty  condition  the  free  consumption  of 
water  apart  from  meals  is  most  desirable. 

Only  a  small  quantity  of  fluid  should  be  taken  during 
meals,  but  during  the  day  from  two  to  three  pints  of  some 
pure  water  should  be  taken.  In  many  cases  the  ordinary 
tap-water  answers  perfectly  well ;  but  if  it  should  happen 
to  be  too  hard  a  water,  or  of  doubtful  purity,  then  some 
simple  water  such  as  still  Salutaris,  Contrexeville,  etc., 
may  be  taken. 

"  Imperial  drink "  constitutes  an  excellent  febrile 
drink  for  the  gouty,  and  in  cases  of  chronic  gout  may 
advantageously  be  taken  when  the  urine  is  high-coloured 
and  when  it  deposits  amorphous  urates  on  cooling.  It  is 
made  by  dissolving  a  teaspoonful  of  powdered  cream  of 
tartar  (potassium  bitartrate)  in  an  imperial  pint  of  water 
or  barley-water,  and  then  sweetening  to  taste  with  loaf- 
sugar  which  has  been  flavoured  by  rubbing  against .  the 
rind  of  a  fresh  lemon.  In  place  of  the  sugar,  an  ounce 
and  a  half  of  syrup  of  lemon  may  be  added  to  the  pint  of 
liquid.  In  cases  of  obese  individuals  the  drink  should  be 
sweetened  with  saccharin  or  saxin  in  place   of   the   sugar. 

The  question  of  alcohol  is  fully  dealt  with  in  the  next 
chapter. 

Simplicity  of  meals. — The  diet  of  gouty  patients  should 
be  simple,  that  is,  the  meals  should  not  be  made  up  of  too 
many  articles.  Simplicity  of  food  means  facility  of  digestion. 
Moderation  in  both  eating  and  drinking  is  perhaps  one  of  the 
most  essential  points  to  insist  on  in  the  dietary  of  the  gouty. 
Certainly  meat,  even  red  meat,  should  not  be  excluded  from 
the  diet.  No  class  of  food-stuff,  as  I  have  said,  is  so  pro- 
ductive of  energy  as  animal  food  ;  and  as  most  cases  of 
chronic  gout  are  suffering  from  lowered  vitality  and  want 
of  tone,  animal  food,  at  all  events  in  moderate  quantity, 


254  GOUT:    TREATMENT.  [partiv. 

is  distinctly  indicated.  My  experience  supports  the  truth 
of  this  view,  as  I  advise,  in  the  great  majority  of  cases 
of  chronic  gout,  the  taking  of  one  meat-meal  a  day.  The 
exclusion  of  any  article  of  diet  or  of  any  class  of  food, 
without  taking  into  account  the  surroundings  of  the  case 
and  the  peculiarities  of  the  individual,  is  unscientific. 
Those  articles  of  diet  that  are  known  in  the  individual 
to  favour  intestinal  fermentation  and  putrefaction  should 
be  avoided,  and,  speaking  generally,  a  sense  of  discomfort 
after  a  meal  indicates  that  some  article  or  articles  of 
food  have  been  taken  which  are  not  beneficial  to  the  indi- 
vidual in  his  present  condition. 

If  the  gouty  symptoms  are  due  to  over-production  of 
toxic  material  from  faulty  intestinal  and  hepatic  meta- 
bolism, and  if  at  the  same  time  the  kidneys  are  sound, 
then  a  diet  which  mainly  consists  of  animal  food  is  in- 
dicated, and  in  extreme  cases  of  this  class  even  the  so- 
called  "  Salisbury  diet  "  may  be  useful.  If,  on  the  other 
hand,  the  symptoms  are  due  to  defective  elimination  on 
account  of  diseased  kidneys,  then  a  diet  which  is  more 
vegetarian  will  be  best.  The  value  of  the  so-called  "  Salis- 
bury diet  "  consists  in  the  small  amount  of  energy  necessary 
for  the  digestion  of  so  simple  a  diet,  and  in  the  fact  that 
it  contains  little  which  can  set  up  intestinal  fermentation 
or  putrefaction.  On  the  other  hand,  a  strictly  vegetarian 
diet  requires  more  digestive  energy  than  a  purely  animal 
one,  and  a  much  larger  quantity  of  vegetable  food  must 
be  taken  to  produce  an  equal  nutritive  effect. 

In  connection  with  the  question  of  the  amount  of  food 
necessary  for  the  maintenance  of  the  most  perfect  health, 
it  is  very  important  to  bear  in  mind  the  necessity  of 
adopting  the  habit  of  thorough  mastication  and  insali- 
vation  of  food.  This  applies  not  only  to  the  gouty,  but 
to  everyone.  The  thorough  mastication  and  insalivation 
of  food  has  a  very  striking  effect  upon  the  appetite,  lead- 
ing to  the   choice  of  a  more  simple  dietary  and   enabling 


Chap.  XIV.]  DIET.  255 

it  to  be  satisfied  with  a  diet  which  is  considerably  less  in 
amount  than  the  ordinary  habit  of  incomplete  mastication 
demands. 

If,  during  the  treatment  of  gout,  an  attack  of  gouty 
dyspepsia  should  at  any  time  intervene,  then  a  milk  diet 
should  be  employed  until  the  dyspeptic  symptoms  have 
abated. 

The  "Salisbury  diet." — As  previously  stated,  as  little 
complexity  as  is  possible  in  the  meals  is  the  main  desider- 
atum in  the  dietary  of  the  gouty,  and  in  a  few  intractable 
cases  of  chronic  gout  it  may  even  become  necessary  to 
reduce  the  dietary  for  a  time  to  the  simplest  possible 
form,  namely,  to  two  articles  of  food  —  lean  meat  and 
water.  There  are  a  few  cases  of  chronic  gout  which  un- 
doubtedly improve,  and  even  recover,  on  an  exclusive 
diet  of  red  meat  and  hot  water.  These  are  generally  cases 
of  chronic  gouty  arthritis  which  have  failed  to  yield  to 
the  ordinary  methods  of  treatment,  and  which  are  accom- 
panied by  dyspepsia,  flatulence,  acid  eructations,  pyrosis, 
and  offensive  stools.  I  have  successfully  treated  a  few 
such  carefully-selected  cases  of  chronic  gout  by  the  employ- 
ment of  this,  the  so-called  "  Salisbury  "  treatment.  It  is 
essential,  before  placing  a  patient  on  such  diet,  that  the 
urine  should  be  carefully  examined,  as  any  advanced 
condition  of  kidney  disease  contra-indicates  the  employ- 
ment of  such  a  dietary.  If  the  evidence  of  kidney  derange- 
ment is  only  slight,  the  adoption  of  the  dietary  is  not 
contra-indicated  ;  but  the  urine  must  be  carefully  exam- 
ined every  two  or  three  days,  as  any  considerable  increase 
in  the  albuminuria  would  at  once  be  an  indication  for  the 
discontinuance  of  this  special  diet.  Gouty  patients  suffer- 
ing from  organic  heart-disease  with  any  failure  of  com- 
pensation should  never  be  placed  on  this  dietary.  The 
dietary  consists  in  the  patient  drinking  from  three  to  five 
pints  of  hot  water  daily,  the  water  being  taken  from  one 
hour  to  one  hour  and  a  half  before  each  meal,  and  half  an 


256  GOUT:    TREATMENT.  [partiv. 

hour  before  retiring  to  rest,  and  eating  from  two  to  four 
pounds  of  beefsteak  daily.  The  meat  should  be  freed  from 
fat,  gristle,  and  connective  tissue,  thoroughly  minced,  mixed 
with  a  little  water,  and  then  warmed  through  with  gentle 
heat  until  it  becomes  brown  in  colour.  A  little  salt  and 
pepper  may  be  added,  and  the  meat  eaten  in  this  form 
or  made  up  into  cakes  and  cooked  on  the  grill.  Later  on 
in  the  treatment,  part  of  the  steak  may  be  taken  grilled, 
or  a  grilled  lean  mutton-chop  may  be  substituted  for  one 
of  the  daily  meals.  The  course  of  treatment  should  last 
for  from  four  to  twelve  weeks,  after  which  a  gradual  return 
to  ordinary  diet  should  be  made. 

Articles  of  diet  to  be  avoided  by  the  g-outy.— 
Rich  meat-soups  —  ox-tail,  turtle,  mock  turtle,  kidney, 
mulligatawny,   hare,  giblet. 

Salmon,  mackerel,  eels,  lobster,  crab,  mussel,  salted 
fish,  smoked  fish,  preserved  fish,  tinned  fish. 

Duck,  goose,  pigeon,  high  game. 

Meats  cooked  a  second  time.  Hare,  venison,  pork, 
lean  ham,  liver,  kidney  ;  salted,  corned,  or  cured  meats, 
pickled  meats,  preserved  and  potted  meats ;  sausages  ; 
all  articles  of  food  pickled  in  vinegar  ;  all  highly-seasoned 
dishes  and  rich  sauces. 

Tomatoes,  beetroot,  cucumber,  rhubarb,  mushrooms, 
truffles. 

Rich  pastry,  rich  sweets,  new  bread,  cakes,  nuts,  dried 
fruits,  ices,  ice-cream. 

Diet  in  chronic  grout  and  for  grouty  subjects.— 
The  following  plan  gives  an  indication  of  the  diet  to  be 
recommended  to  gouty  subjects  : — 

Morning. — Half  a  pint  to  a  pint  of  hot  water,  flavoured 
with  a  slice  of  lemon-peel,  should  be  slowly  sipped  imme- 
diately on  rising. 

Breakfast. — A  selection  may  be  made  from  the  follow- 
ing articles  of  diet,  according  to  the  taste  of  the  patient  : — 
Porridge    and   milk,    whiting,    sole,    or   plaice,    fat   bacon. 


Chap.  XIV]  DIET.  257 

eggs  cooked  in  various  ways,  dry  toast  or  "  Zwieback 
bread,"  thinly  buttered,  and  tea  infused  for  three  minutes 
and  then  strained  from  the  leaves.  Fat  bacon  is  digestible 
when  grilled,  but  less  so  when  boiled.  Eggs  should  not 
be  taken  hard-boiled. 

Lunch  and  Dinner. — Soups  suitable  for  the  gouty  are 
vegetable  purees,  and  soups  made  by  boiling  beef  or  mutton 
bones  with  vegetables,  and  subsequently  removing  the 
fat  which  separates  on  cooling.  These  soups  should  not 
be  thickened  with  farinaceous  substances. 

The  varieties  of  fish  most  suitable  to  the  gouty  are 
whiting,  sole,  turbot,  plaice,  smelt,  flounder,  grey  mullet, 
and  fresh  haddock. 

The  birds  that  are  admissible  as  articles  of  diet  are 
chicken,  pheasant,  turkey,  and  game  (not  high). 

Butcher's  meat,  mutton,  lamb,  and  beef  should  be 
taken  at  only  one  meal  in  the  day,  and  then  in  moderate 
quantity.  Two  vegetables  may  be  taken  at  both  lunch 
and  dinner.  Any  of  the  ordinary  vegetables  may  be 
taken,  except  those  previously  mentioned  as  best  avoided  ; 
but  those  that  I  consider  most  likely  to  prove  beneficial 
to  gouty  subjects  are  spinach,  Brussels  sprouts,  French 
beans,  winter  cabbage,  Savoy  cabbage,  turnip  tops,  turnips, 
and  celery.  Potatoes  may  also  be  taken  in  moderate 
quantities.  Stewed  fruits,  or  baked  apples  or  pears,  may 
be  taken  every  day  at  one  meal. 

Green  vegetables  as  salads  may  be  taken,  provided  oily 
dressings  are  avoided.  A  simple  savoury  may,  if  desired, 
be  taken  at  the  end  of  dinner,  or  a  small  quantity  of  cheese, 
if  well  masticated,  and  if  free  from  the  penicillium  fungus 
or  mould. 

Night. — Half  a  pint  to  a  pint  of  hot  water,  flavoured 
with  a  slice  of  lemon-peel,  should  be  slowly  sipped  before 
retiring  to  bed. 

With  regard  to  persons  who  are  disposed  to  gout,  but 
are  not  actually  suffering  from  it,  the  usual  mixed  diet 


258  GOUT:    TREATMENT.  [Partiv. 

may  be  taken,  but  they  should  hmit  the  starchy  articles 
of  food,  and  should  avoid  all  rich  sweets,  rice,  tapioca, 
and  sago.  Thin  and  ill-nourished  subjects  require  modi- 
fications in  their  diet  as  compared  with  people  who  are 
stout,  while  those  who  take  plenty  of  exercise  can  take 
food  forbidden  to  the  sedentary. 

Individuals  who  especially  benefit  by  a  reduction  of 
diet,  both  as  regards  quantity  and  quality,  are  those  over- 
fed people  who  are  past  middle  life. 


CHAPTER     XV. 

ALCOHOL   IN   GOUT. 

Alcoholic  drinks  —  Acidity  and  gout -inducing  power  of  wines 
and  beers — Cause  of  the  inducement  of  gout  by  wines 
and  beers — Wines  least  injurious  to  the  gouty — Cider — 
Perry. 

Alcoholic  drinks.  —  Stated  as  a  general  principle,  a 
person  who  is  subject  to  gout  is  better  without  alcohol  in 
any  form.  There  are,  however,  some  who  require  a  little 
alcohol,  either  to  aid  digestion  or  to  enable  them  to  get 
through  their  work  ;  and  here  I  am  entirely  in  accord 
with  the  advice  given  by  Goodhart,  that,  if  a  man  requires 
any  stimulant  at  all,  it  is  a  matter  he  must  decide  by  experi- 
ment for  himself,  for  no  medical  man  can  tell  him.  If 
alcohol  is  necessary  or  desirable,  the  form  in  which  it  is  to  be 
taken  is  frequently  a  matter  whjch  the  patient  can  decide 
better  than  the  medical  man  ;  but  I  would  insist  upon  the 
importance  of  definitely  limiting  the  amount  to  be  taken, 
and  of  restricting  its  consumption  absolutely  to  meals. 
Some  patients  find  that  a  little  whisky  or  brandy  suits  them 
best  ;  others  find  a  light  still  Moselle  preferable  ;  a  few, 
but  in  my  opinion  only  a  very  limited  number,  find  a  light 
claret  agrees  best  with  them.  Champagne  is  a  wine 
which  is  seldom  suited  to  the  gouty,  especially  if  taken 
daily.  In  elderly  people  or  in  the  feeble,  a  moderate 
amount  of  pure  whisky  undoubtedly  docs  good  ;  but  the 
indiscriminate  ordering  of  whisky  to  gouty  subjects  is,  I 
am  sure,  wrong. 

It  is  well  known  that  certain  alcoholic  drinks  injuriously 
affect  the  gouty  process,  whilst  others  exert  a  less  injurious 

259 


26o  GOUT:    TREATMENT.  [partiv. 

influence.  Alcoholic  drinks  which  have  been  obtained  by 
fermentation,  but  which  have  not  been  submitted  to  dis- 
tillation, such  as  wines  and  beers,  appear  to  exercise  a  more 
harmful  influence  than  if  the  same  amount  of  alcohol  be 
consumed  in  the  form  of  one  of  the  distilled  spirits,  such 
as  whisky,  brandy,  etc.  Sir  Alfred  Garrod  considers  that 
the  reason  for  the  prevalence  of  gout  in  the  south  of 
England  and  its  rarity  in  Scotland  is  chiefly  to  be  found 
in  the  difference  between  the  beverages  drunk  in  the  two 
countries. 

Acidity  of  wines  and  beers. — Distilled  spirits  contain 
little  or  no  acid,  whilst  wines  and  beers  are  distinctly  acid  ; 
and  to  the  acids  contained  in  these  drinks  many  physicians 
have  attributed,  and  still  do  attribute,  their  gout-producing 
properties.  The  acids  present  are  tartaric,  succinic,  malic, 
acetic,  formic,  propionic,  butyric  and  oenanthic.  The 
acidity  of  wines  is  mainly  due  to  tartaric,  malic,  and  suc- 
cinic acids.  The  amount  of  free  acid  in  sound  wine,  reckoned 
as  tartaric  acid,  varies  between  0.3  and  0.7  per  cent.  I 
found  the  acidity  of  some  1847  port,  reckoned  as  tartaric  acid, 
to  be  0.6  per  cent.  Cider  owes  its  acidity  mainly  to  malic 
acid.  Its  total  acidity  is  usually  o.i  per  cent.  If  we 
arrange  the  various  wines  in  (a)  their  order  of  acidity  and 
(b)  the  order  of  their  gout-inducing  power,  we  find  that  the 
most  acid  wines  are  not  those  which  most  predispose  to 
gout  (Table  LIX.).  The  arrangement  of  wines  and  beers 
in  the  order  of  acidity,  beginning  with  the  most  acid,  is 
that  given  by  Bence  Jones,  while  the  arrangement  in  order 
of  their  gout-inducing   power  is  that  given  by  Sir  Alfred 

Garrod. 

Hock,  Moselle,  and  the  weaker  kinds  of  ales  have  com- 
paratively little  gout-inducing  power. 

The  acidity  of  alcoholic  liquors  cannot  have  much 
influence  in  determining  an  attack  of  gout,  as  port,  sherry 
and  malt  liquors,  which  are  the  most  powerful  predisposing 
agents,  are  amongst  the  least  acid,  whilst  the  more  acid 


Chap.  XV]  ALCOHOL.  261 

wines  are  comparatively  harmless  in  this  respect  ;  more- 
over, it  must  be  remembered  that  the  organic  acids  and 
their  salts  contained  in  wines  are  converted  in  the  body 
into  alkaline  compounds,  and  are  excreted  in  the  urine  as 
such. 

TABLE  LIX. 
wines  and  beers  arranged  in  order  of  acidity  and  gout-inducing  power. 


(a)  Acidity  (beginning  with  the 

(b)  Gout-inducing  power  (beginning 

most  acid). 

with  the  most  powerful). 

Moselle 

Port 

Rhine  wines 

Sherry 

Burgundy 

Other    stronger    wines 

Madeira 

Champagne 

Claret 

Stout  and  porter 

Champagne 

Strong  ales 

Port 

Claret 

Sherry 

Hock 

Malt  liquors 

Moselle 

Weaker  kinds  of  ales 

Gout-inducing"    properties    of    alcoholic    drinks.  — 

The  question  is — To  what  constituent  or  constituents  of 
wines  and  beers  are  their  gout-inducing  properties  due  ? 
They  are  not  due  to  the  alcohol  alone,  for  in  countries  such 
as  Scotland,  Norway,  Sweden  and  Poland,  where  distilled 
spirits  are,  or  were,  freely  consumed,  gout  is  almost  un- 
known. Moreover,  several  experiments  that  I  have  made 
indicate  that  alcohol,  in  such  quantities  as  are  ever  likely 
to  be  present  in  the  blood,  has  no  effect  either  upon  the  con- 
version of  sodium  quadriurate  into  biurate  or  on  the  solu- 
bility of  the  latter.  The  gout-inducing  properties  are 
most  probably  not  due  to  the  acids  of  the  wines  and  beers, 
for  the  reasons  which  have  already  been  given.  It  is 
also  very  doubtful  whether  the  sugar  present  in  wines  is 
per  se  harmful ;  but  as  a  rule  the  sweet  wines  are  fortified 
wines,  while  the  natural  wines  are  generally  dry.  It  is  very 
probable  that  the  sweet  fortified  wines  are  prone  to  produce 


262  GOUT:    TREATMENT.  [partiv. 

fermentative  and  catarrhal  changes  in  the  gastro-intestinal 
tract,  and  are  on  that  account  harmful  to  the  gouty. 

The  gout-inducing  properties  are  certainly  not  directly 
due  to  the  cenanthic  ether  and  other  ethereal  salts  of  wines 
exerting  any  effect  either  on  the  rate  of  decomposition 
of  the  sodium  quadriurate  or  on  the  solubility  of  the  biurate. 
To  demonstrate  these  points,  I  have  extracted  from  old  port 
wines  the  ethereal  salts  to  which  the  bouquet  of  the  wines 
is  due,  and  have  experimented  with  these  ethereal  com- 
pounds on  the  quadriurates  and  biurates.  Using  quantities 
far  in  excess  of  those  likely  to  be  present  in  the  blood  after  the 
moderate,  or  even  immoderate,  consumption  of  such  wine, 
I  find  that  none  of  these  volatile  constituents  exercises  the 
slightest  effect  either  in  hastening  the  decomposition  of 
the  sodium  quadriurate  or  in  diminishing  the  solubility 
or  hastening  the  precipitation  of  sodium  biurate.  As  to 
the  modus  operandi  of  certain  wines,  such  as  port,  etc., 
in  hastening  an  attack  of  gout,  I  incline  to  the  opinion  that 
the  influence  of  wines  on  the  development  of  gout  is  in  great 
part  due  to  the  effect  they  exercise  in  producing  fermenta- 
tive and  catarrhal  changes  in  the  gastro-intestinal  tract, 
and  in  also  injuriously  affecting  hepatic  metabolism.  At 
the  same  time,  it  must  be  remembered  that  those  accus- 
tomed to  drink  wine  are  also  able  to  indulge  in  other  luxuries 
of  the  table  which  greatly  favour  the  development  of  gout. 

As  Woods  Hutchinson  has  pointed  out,  the  experiments 
of  Boix  appear  to  have  shown  that,  in  the  case  of  alcohol, 
it  is  not  the  direct  toxic  effect  of  the  drug,  so  much  as  the 
catarrhal  and  other  irritative  changes  set  up  by  it  in  the 
intestines,  which  produce  the  poisonous  products  that  are 
carried  to  the  liver  and  cause  the  irritation  and  degenera- 
tion of  that  organ.  In  other  words,  unless  alcohol  is 
taken  in  sufficient  amounts  to  disturb  gastric  and  intestinal 
digestion,  it  will  not  produce  the  hob-nail  liver. 

Another  consideration  to  be  borne  in  mind  is  the  rapidly 
fermentable  fruit  and  malt  sugars,  esters,  and  higher  alcohols, 


Chap.  XV.j  ALCOHOL.  263 

which  are  also  present  in  wines  and  beers,  and  which  experi- 
ence in  gout  shows  are  more  closely  concerned  with  fer- 
mentative changes  in  the  stomach  and  intestines  than  is  the 
alcohol  itself. 

Port  is  a  wine  which  is  especially  unsuited  to  the  majority 
of  gouty  subjects.  The  gout-inducing  properties  of  the  wine 
are,  I  believe,  mainly  dependent  upon  the  ethereal  com- 
pounds which  give  the  aroma  or  bouquet  to  the  wine, 
although  these  bodies  do  not  act  directly  on  either  the  quad- 
riurate  or  biurate  of  sodium.  If  this  view  is  correct  it  would 
explain  the  well-known  fact  that  old  and  matured  ports  are 
much  more  provocative  of  gout  than  comparatively  new 
ports  taken  direct  from  the  wood.  The  development  of  the 
ethereal  compounds  in  the  wine  extends  over  many  years, 
and  especially  progresses  after  the  wine  is  laid  by  in  bottles. 
In  a  few  cases  of  asthenic  gout,  especially  in  old  people, 
a  moderate  amount  of  comparatively  new  port  taken  direct 
from  the  wood  undoubtedly  does  good. 

In  my  opinion  the  wines  which  are  least  injurious  as  a  rule 
to  gouty  subjects  to  whom  it  is  found  necessary  to  order  a 
small  amount  of  wine  are  the  light  still  white  wines,  such  as 
Moselle,  certain  French  wines,  certain  Austrian  wines,  hock, 
and  a  few  of  the  lighter  Austrahan  and  Calif ornian  wines. 
These  last,  owing  to  their  greater  alcoholic  strength,  should 
be  taken  diluted  with  water  or  some  mineral  water. 

Gouty  subjects  suffering  from  glycosuria  or  diabetes 
should  entirely  abstain  from  alcoholic  drinks,  unless  marked 
debihty  and  loss  of  appetite  necessitates  the  restricted 
administration  of  them.  Gouty  persons  subject  to  attacks 
of  eczema  are  also  much  better  without  alcohol  in  any  form. 

"  Rough  "  cider,  that  is  the  completely  fermented  apple- 
juice,  taken  in  moderation,  agrees  well  with  most  gouty 
subjects.  It  contains  but  a  small  percentage  of  alcohol,  is 
free  from  sugar,  and  its  acidity  is  chiefly  due  to  malic  acid, 
which  passes  into  the  circulation  in  the  form  of  alkaline 
malates,  which  in  their  turn  are  converted  in  the  kidneys 


264  GOUT:    TREATMENT.  [Partiv. 

into  alkaline  carbonates  and  excreted  as  such,  thereby 
increasing  the  elimination  of  urates.  The  bottled  or 
"  champagne  "  cider,  which  is  imperfectly  fermented, 
should  never  be  used  by  gouty  individuals,  owing  to  its 
undoubted  liability  to  set  up  gastro-intestinal  fermenta- 
tions. Dry  or  "  rough  "  cider  mixed  with  an  equal  quantity 
of  an  aerated  water  is  an  excellent  beverage  for  the  gouty. 
Dry  perry  is  also  a  suitable  drink  for  the  subjects  of  gout. 


CHAPTER    XVI. 

SPA,   BALNEOLOGICAL,  AND   CLIMATIC   TREATMENT. 

Spa  treatment  —  Ionic  theory  and  Radio-activity — The  uses 
of  mineral  waters  in  the  treatment  of  gout — Classification 
of  mineral  waters — The  simple  waters — Simple  alkaline 
waters — Alkaline  sulphated  waters — Alkaline  muriated 
waters — Common  salt  or  muriated  waters — Sulphur  waters 
— Hot  and  cold  mineral  waters — Choice  of  a  spa — Balneology 
—Climatic  Treatment. 

Spa  treatment. — The  free  employment  of  water  in  the 
treatment  of  gout  dates  from  ancient  times.  At  the 
Temples  of  Asklepios  at  Epidaurus  and  Athens  water  was 
used  extensively  both  internally  and  externally,  and  active 
gymnastic  exercise,  riding,  friction  of  the  skin,  massage, 
and  counter-irritation  were  prescribed. 

Spa  treatment  is  a  complex  treatment  made  up  of  several 
factors,  and  on  the  correct  apportionment  of  these  different 
factors  depends  much  of  the  successful  issue  of  the  treat- 
ment. These  several  factors  are  (i)  hydrotherapy,  which 
includes  the  taking  of,  and  the  bathing  in,  the  waters  ; 
(2)  diet ;  (3)  exercise  ;  and  (4)  accessory  forms  of  treat- 
ment, such  as  electric  light  baths,  electrical  treatment, 
massage,  etc.  With  regard  to  the  drinking  of  a  water  at  a 
spa  there  is  a  tendency  with  some  medical  men  to  consider 
that  the  efficacy  of  a  natural  mineral  water  is  due  solely 
to  its  watery  constituent — in  other  words,  that  its  one 
therapeutic  use  is  that  of  a  flushing  agent.  Even  so 
astute  a  physician  as  the  late  Sir  William  Roberts  appears 
to  have  held  this  view.  In  his  Croonian  lectures,  referring 
to  the  employment  of    the  waters   of   certain  spas   in  the 

265 


266  GOUT:    TREATMENT.  [partiv. 

treatment  of  gout,  he  said  : — "  Now  there  can  be  no  reason- 
able doubt  that  the  efficacy  of  these  springs  has  nothing 
to  do  with  their  scanty  mineral  ingredients  but  depends  on 
their  watery  constituent.  .  .  .  Their  action  would  be 
to  temporarily  dilute  the  blood  and  lower  its  percentage 
of  urates  and  sodium  salts.  This  effect  would  tend  to  re- 
tard or  prevent  uratic  precipitation,  and  thus  give  the 
defective  kidneys  additional  time  to  overtake  their  arrears 
in  the  task  of  ehminating  uric  acid." 

Ionic  theory  and  radio-activity.  —  If  the  efficacy 
of  a  natural  mineral  water  depended  solely  on  its  watery 
constituent  I  do  not  for  one  moment  think  that  the  resort 
of  sufferers  to  the  various  natural  springs  would  have 
successfully  stood  the  test  of  centuries  as  it  undoubtedly  has. 
The  fact  is  that  in  judging  of  the  effect  of  natural  mineral 
waters  we  have  been  too  much  under  the  domination  of 
analytical  chemistry,  and  that  our  deductions  from  these 
results  have  been  consequently  biased  and  cramped.  The 
more  I  consider  the  therapeutic  effects  of  the  natural 
mineral  waters  the  more  convinced  I  am  that  chemical 
analysis,  although  it  can  inform  us  what  are  the  mineral 
constituents  of  the  natural  waters,  is  yet  unable  to  deter- 
mine exactly  the  state  of  the  salts  dissolved  in  them.  The 
"  ionic  or  electrical  dissociation  theory  "  and  the  exist- 
ence of  the  mineral  constituents  of  natural  waters  as  "  ions  " 
are  leading  our  thoughts  to  a  new  and,  I  believe,  correct 
appreciation  of  the  therapeutic  values  of  these  waters. 

An  element  or  a  group  of  elements  divorced  from  the  rest 
of  the  original  molecule  is  an  "  ion."  According  to  the  ionic 
theory  metallic  salts  in  very  dilute  solutions  are  completely 
split  up  into  their  "  ions,"  so  that  all  the  properties  of  these 
solutions  must  be  the  sum  of  the  properties  of  the  separate 
"  ions."  In  concentrated  solutions  much  of  the  salt  remains 
in  the  undissociated  state  and  only  a  small  proportion  in  the 
form  of  dissociated  "  ions,"  whereas  in  most  of  the  natural 
mineral   waters,   which   are   weak   solutions   of  salts,    the 


Chap.  XVI.]  IONIC    THEORY.  267 

mineral  constituents  are  mainly,  if  not  entirely  in  many 
waters,  in  the  form  of  "  ions,"  and  in  this  form  the  thera- 
peutic effects  and  potency  may  be  quite  different  from  those 
of  the  undissociated  salts.  Ionic  dissociation  does  not,  there- 
fore, alter  the  percentage  composition  of  a  salt,  but  may  very 
materially  alter  its  therapeutic  properties,  so  that  in  all 
probability  the  "  ions  "  rather  than  the  salts  are  responsible 
in  great  part  for  the  effects  of  mineral  waters. 

In  intimate  relation  with  this  aspect  of  the  matter  is  the 
question  of  radio-activity  in  hydrotherapy.  Our  conception 
of  the  atom  as  an  indivisible  and  finite  body  is  disappearing, 
and,  in  view  of  the  recent  discoveries  that  have  been  made  in 
connection  with  radio-activity,  the  atom  must  be  conceived 
as  consisting  of  an  aggregate  of  corpuscles,  and  each  atom 
has  associated  with  it  a  definite  charge  of  electricity,  such  an 
electrically  charged  atom  being  an  "  ion."  The  smallest  unit 
of  electric  charge  is  known  as  an  "  electron,"  and  the  atom 
is  charged  with  a  number  of  these  electrons,  which  are  in  a 
state  of  vigorous  motion  among  themselves  within  the  atom. 
Radio-activity  consists  in  the  flinging  away  with  great 
violence  of  actual  atoms.  The  substance  left  is  also  radio- 
activity, and  ultimately  one  of  the  residues  seems  to  dis- 
charge electrons  instead  of  atoms  of  matter,  thus  effecting  a 
transmutation  of  matter. 

Now,  most,  if  not  all,  of  the  natural  mineral  waters 
which  have  been  examined  have  been  found  to  be  distinctly 
radio-active,  and  the  lower  the  mineralisation  of  the  water 
the  more  intense  is  its  radio-activity.  In  this,  I  think,  lies 
the  explanation  of  the  fact  that  an  artificially  prepared 
mineral  water,  although  it  may  be  made  identical  in  chemical 
composition  with  the  natural  one,  does  not  possess  the  same 
therapeutic  effects  as  the  natural  water,  since  it  is  lacking, 
at  all  events  to  any  appreciable  extent,  in  the  property  of 
radio-activity.  A  natural  water  at  the  moment  of  its 
discharge  from  the  earth  is  radio-active,  whereas  an  ordinary 
drinking    water    does    not    possess    this    property   in    an 


268  GOUT:    TREATMENT.  tPARtiV. 

appreciable  degree.  Hence  also  the  desirability  of  drinking 
the  water  at  its  source,  since  by  the  bottling  and  keeping  of 
a  natural  water  the  radio-activity  is  to  a  great  extent  lost. 
When  we  consider  the  marked  influence  of  radio-active 
emanations  on  new  growths  and  various  morbid  tissues,  is 
it  too  remarkable  to  conceive  that  a  radio-active  mineral 
water  will  exercise  a  potent  effect  on  those  morbid  changes 
within  the  body  which  are  connected  with  abnormal  tissue 
metabolism  ? 

Uses  of  mineral  waters  in  the  treatment  of  gout.— 
If  gout  is  primarily  due  to  the  absorption  of  toxins  from 
the  intestinal  canal  dependent  upon  a  catarrh  of  the  intes- 
tinal mucosa,  many  of  the  natural  mineral  waters  must  be 
efficacious  in  altering  the  catarrhal  condition  and  in  im- 
proving the  digestive  processes  ;  also  the  secondary  effect  of 
increasing  the  flow  of  bile  and  of  thoroughly  washing  out  all 
the  tissues,  so  as  to  get  rid  of  toxic  accumulation,  is  impor- 
tant. 

The  value  of  a  given  mineral  water  in  the  treatment 
of  gout  depends  greatly  on  the  main  object  with  which  it 
is  taken.  For  instance,  it  may  be  taken  to  remove 
gouty  deposits,  or  to  stimulate  the  action  of  a  sluggish 
liver  and  to  relieve  portal  congestion,  or  for  the  treatment 
of  gouty  dyspepsia,  or  to  relieve  the  bowels  in  cases  of 
torpor  and  gastro-intestinal  catarrh,  or  to  act  on  the  kidneys, 
or  to  relieve  gouty  affections  of  the  skin.  Now  it  is  mani- 
fest that  any  one  mineral  water  is  not  likely  to  produce 
all  these  effects,  and  it  is  also  obviously  conceivable  that 
a  mineral  water  which  might  be  most  useful  to  effect  one 
of  these  purposes  might  prove  injurious  if  employed 
to  effect  another.  No  doubt  considerable  error  has  arisen 
from  indiscriminately  sending  gouty  patients  to  a  particular 
spa,  without  giving  due  consideration  to  the  question  as  to 
whether  the  water  of  that  spa  is  suitable  for  the  treatment 
of  the  specific  gouty  disorder  from  which  the  patient  is 
suffering.     It  is  well  to  bear  in  mind  that  a  patient  should 


chxp.xvi]  mineral    waters.  269 

not  be  sent  to  a  spa  during  the  acute  stage  of  gout,  nor  if 
suffering  from  marked  organic  disease  of  the  heart  or 
kidneys. 

It  is  especially  in  cases  of  chronic  gout,  of  gastro-intes- 
tinal  catarrh  and  torpor,  of  gouty  dyspepsia,  sluggish  action 
of  the  liver,  gouty  eczema,  gouty  glycosuria,  and  of  other 
forms  of  irregular  gout,  that  mineral  waters  prove  so  valuable, 
whilst  the  various  baths,  combined  with  massage,  are  very 
useful  in  producing  softening  and  absorption  of  the  deposits 
in  the  joints  and  other  tissues. 

The  explanations  given  as  to  the  modus  operandi  of  a 
particular  mineral  water  must  sometimes  be  received 
with  a  certain  amount  of  caution.  For  instance,  the 
advocates  of  one  mineral  water  will  extol  its  efficacy  in 
the  treatment  of  gout  on  account  of  the  lime  salts  con- 
tained in  it  and  its  freedom  from  sodium  salts,  whilst,  on  the 
other  hand,  the  advocates  of  another  mineral  water  will 
insist  that  the  large  quantities  of  sodium  salts  present  in 
it  and  the  absence  of  lime  salts  are  the  potent  factors 
in  its  usefulness  in  the  treatment  of  gout. 

With  regard  to  the  presence  of  lime  salts,  a  mineral 
water  containing  such  does  not  exercise,  by  virtue  of  those 
lime  salts,  either  a  deleterious  or  a  beneficial  action  on  the 
gouty  deposits  of  sodium  biurate.  The  only  objection  to 
a  water  containing  a  large  quantity  of  lime  salts  is  the 
tendency  to  produce  digestive  disturbances  and  to  cause 
constipation. 

CLASSIFICATION    OF   MINERAL   WATERS. 

The  various  mineral  waters  used  in  the  treatment  of 
gout  may  be  classified  according  to  their  chemical  composi- 
tion into  the  six  following  groups  : — 

1.  The  simple  waters,  or  waters  comparatively  free  from 
sodium  salts. 

2.  The  simple  alkaline  waters. 

3.  The  alkaline  sulphated  waters. 


270 


GOUT:    TREATMENT. 


[Part  IV. 


4.  The  alkaline  muriated  waters. 

5.  The  common  salt  or  muriated  waters. 

6.  The  sulphur  waters. 

1.  The  simple  waters,  op  waters  comparatively 
free  from  sodium  salts. — These  are  the  waters  that  are 
especially  likely  to  prove  useful  for  the  removal  of  uratic 
deposits  in  the  joints  and  tissues.  They  contain  small  pro- 
portions of  calcium  carbonate  and  calcium  sulphate,  but  the 
quantities  of  sodium  salts  present  are  so  small  that  for  all 
practical  purposes  they  may  be  neglected.  The  following 
table  (Table  LX.)  shows  the  proportions  of  sodium  salts 
in  the  respective  waters  of  this  class,  represented  as 
grains  of  sodium  per  gallon  : — 

TABLE  LX. 

Showing    the    proportions  of  sodium  salts,   represented  as  grains  of 
sodium  per  gallon,  in  the  principal  simple  waters. 


Mineral  water. 

Grains  of  sodium 
per  gallon. 

Teplitz 

0.20 

Strathpeffer 

0.45 

Contrexeville 

0.79 

Buxton 

1.47 

Pfaefers    . 

1. 61 

Gastein     . 

5.89 

Wildbad  . 

7-6Z 

Bath 

9.42 

Vittel 

13-39 

Teplitz  (Bohemia).  The  waters  are  hot  (83°  to  114°  F.). 
Altitude  about  730  feet.  Thermal  baths  and  peat  baths 
are  provided.  Open  all  the  year,  but  the  usual  season 
is  from  May  to  September. 

Strathpeffer  (Scotland,  Ross-shire).  The  waters  are 
cold.  Altitude  about  200  feet.  Strathpeffer  also  pos- 
sesses sulphur  springs  and  a  chalybeate  spring.  Various 
kinds  of  baths  are  provided.     The  sulphur  waters  are  useful 


chap.xvi]  mineral    waters.  271 

in  the  treatment  of  the  various  skin  affections  connected 
with  gout.  Open  all  the  year,  but  the  usual  season  is  from 
May  to  October. 

Contrexc'ville  (France).  The  waters  are  cold.  Altitude 
1,150  feet.  Baths  are  provided.  The  water,  in  addition 
to  being  almost  free  from  sodium  salts,  contains  magnesium 
sulphate,  so  that  it  is  useful  not  only  for  the  removal  of 
uratic  deposits,  but  also  in  the  treatment  of  gastro-intestinal 
and  hepatic  disorders  associated  with  gout,  and  for  the 
treatment  of  urinary  gravel.  The  season  is  from  the 
beginning  of  June  to  the  end  of  October. 

Buxton  (England,  Derbyshire).  The  waters  are  warm 
(82°  F.).  Altitude  1,000  feet.  Baths,  douches,  and  douche- 
massage  are  provided.  The  water  contains  a  considerable 
amount  of  free  nitrogen.  On  account  of  the  very  small 
proportion  of  sodium  salts  present  it  is  an  extremely  benefi- 
cial water  to  employ  with  the  object  of  removing  uratic 
deposits.  The  climate  is  bracing.  Open  all  the  year,  but 
the  season  is  from  April  to  September. 

Pfaefers  (Switzerland).  The  waters  are  warm  (89°  to 
93°  F.).  Altitude  about  1,700  feet.  Baths  are  provided. 
The  season  is  from  May  to  October. 

Gastein  (Austria).  The  waters  are  hot  (78°  to  121°  F.). 
Altitude  3,310  feet.  Baths  are  provided.  The  season  is 
from  the  beginning  of  May  to  the  end  of  September. 

Wildbad  (Germany).  The  waters  are  hot  (91°  to  105°  F.). 
Altitude  about  1,320  feet.  Baths,  douches,  and  electric 
baths  are  provided.  The  season  is  from  the  beginning  of 
May  to  the  end  of  September. 

Bath  (England,  Somersetshire).  The  waters  are  hot 
(104°  to  120°  F.).  Altitude  100  feet.  Excellent  baths, 
douches,  and  douche-massage  are  provided.  The  water  is 
a  very  useful  one  to  employ  with  the  object  of  removing 
uratic  deposits,  and  chronic  affections  of  the  joints  can  be 
well  treated  at  Bath  by  external  methods.  Open  all  the 
year,  but  the  spring  and  autumn  are  the  favourite  seasons. 


272  GOUT:    TREATMENT.  [partiv. 

The  climate  of  Bath  is  mild,   and  it  is  therefore  a  good 
winter  resort. 

Vittel  (France).  The  waters  are  cold.  Altitude  i,ioo 
feet.     The  season  is  from  May  to  September. 

2.  Simple  alkaline  wateps. — These  waters  contain 
sodium  bicarbonate.  They  are  useful  for  gouty  patients 
suffering  from  hepatic  congestion,  dyspepsia,  and  gastro- 
intestinal catarrh.  The  principal  waters  of  this  class 
are  those  of  Vichy,  Vals,  Neuenahr,  Salzbrunn,  Fachingen, 
and  Bilin. 

Vichy  (France).  The  waters  are  hot  (89°  to  110°  F.). 
Altitude  736  feet.  Baths  are  provided.  The  waters  are 
especially  useful  in  the  treatment  of  gouty  dyspepsia  and 
gastro-intestinal  catarrh,  in  cases  of  deranged  hepatic 
function,  and  for  plethoric  gouty  patients  suffering  from 
glycosuria  or  diabetes.  The  cases  best  suited  to  Vichy 
are  gouty  dyspeptics,  fairly  vigorous,  with  a  tendency  to 
pass  acid  urine,  with  deposits  of  urates  and  uric  acid.  It  is 
also  very  efficacious  in  promoting  the  evacuation  of  renal 
(uric  acid)  calculi.  Open  all  the  year,  but  the  season  is 
from  the  middle  of  May  to  the  end  of  September.  In  the 
middle  of  summer  Vichy  is  very  hot. 

Vals  (France).  The  waters  are  cold.  Altitude  300  feet. 
The  waters  may  be  used  for  the  same  class  of  gouty  cases 
as  mentioned  in  connection  with  the  Vichy  waters,  but 
those  springs  containing  iron  should  be  avoided  by  gouty 
patients.  The  season  is  from  the  middle  of  May  to  the 
middle  of  October. 

Neuenahr  (Germany).  The  waters  are  hot  (75°  to 
104°  F.).  Altitude  760  feet.  Baths  are  provided.  The 
waters  may  be  used  for  the  same  class  of  gouty  cases  as 
mentioned  in  connection  with  the  Vichy  waters.  The 
season  is  from  May  to  October,  but  in  the  middle  of  the 
summer  Neuenahr  is  very  hot. 

Salzbrunn  (Prussian  Silesia).  The  waters  are  cold. 
Altitude  1,320  feet.    The  waters  may  be  used  for  the  same 


chap.xvi]  mineral    waters.  273 

class  of  gouty  cases  as  mentioned  in  connection  with  the 
Vichy  waters.  The  season  is  from  the  beginning  of  May 
to  the  end  of  September. 

3.  Alkaline  sulphated  waters. — These  waters  con- 
tain sodium  bicarbonate,  sodium  sulpliate,  and  generally 
a  moderate  proportion  of  sodium  chloride.  They  are 
useful  in  the  treatment  of  gout  connected  with  congestion 
of  the  liver  and  portal  system,  and  of  gout  connected 
with  gastro-intestinal  catarrh  and  with  some  forms  of 
dyspepsia.  They  may  also  be  employed  in  the  treatment 
of  gouty  glycosuria.  The  principal  waters  of  this  class 
are  those  of  Carlsbad,  Marienbad,  Tarasp-Schuls,  Brides- 
les-Bains,  Cheltenham,  Leamington,  and  Bertrich. 

Carlsbad  (Bohemia).  The  Carlsbad  waters  are  rich 
in  sodium  sulphate  and  sodium  bicarbonate,  and  also 
contain  a  moderate  proportion  of  sodium  chloride.  The 
waters  are  hot  (95°  to  162°  F.).  Altitude  1,160  feet.  Baths 
are  provided.  The  waters  are  best  suited  for  gouty  patients 
suffering  from  torpor  of  the  hepatic  and  gastro-intestinal 
functions,  and  especially  for  cases  of  congestive  enlarge- 
ment of  the  liver  with  a  tendency  to  haemorrhoids.  The 
Carlsbad  waters  have  a  remarkable  action  on  the  liver, 
and  they  have  been  especially  utilised  in  the  treatment 
of  gout  associated  with  hepatic  congestion,  haemorrhoids, 
and  "  abdominal  plethora."  They  are  also  of  use  in  the 
treatment  of  gouty  glycosuria.  The  waters  are  best  suited 
for  those  of  fairly  robust  constitutions.  They  are  contra- 
indicated  if  heart  disease  is  present,  or  if  arterio-sclerotic 
changes  are  advanced,  or  if  the  kidneys  are  seriously  impli- 
cated. The  season  is  from  the  middle  of  April  to  the 
end  of  September.  A  course  at  Carlsbad  may  advanta- 
geously be  succeeded  by  a  stay  in  Switzerland  at  a  station 
situated  at  a  high  altitude. 

Marienbad  (Bohemia).  The  waters  are  cold.  Alti- 
tude about  1,980  feet.  Baths  are  provided.  The  waters 
are  very  similar  in  composition  to  those  of  Carlsbad,  and 
s 


274  GOUT:    TREATMENT.  [Partiv. 

are  useful  for  the  same  class  of  cases.  The  season  is  from 
May  to  September.  A  course  at  Marienbad  is  also  advan- 
tageously succeeded  by  a  stay  at  a  high  altitude. 

Tarasp-Schuls  (Switzerland).  The  waters  are  cold. 
Altitude  3,870  feet.  Baths  are  provided.  The  waters 
are  useful  for  the  same  class  of  cases  as  mentioned  in  con- 
nection with  the  Carlsbad  waters.  The  season  is  from 
the  middle  of  June  to  the  middle  of  September. 

Brides-les-Bains  (France.)  The  waters  are  hot  (95°  F.). 
Altitude  about  1,860  feet.  Baths  are  provided.  The 
waters  are  useful  for  the  treatment  of  gouty  dyspepsia 
associated  with  constipation.  The  season  is  from  the 
beginning  of  June  to  the  end  of  September. 

Cheltenham  (Gloucestershire).  The  waters  are  cold. 
They  are  rich  in  sodium  chloride  and  sodium  sulphate  ; 
one  of  them  contains  in  addition  a  large  amount  of  mag- 
nesium sulphate  ;  the  Pittville  or  alkaline  water  contains, 
besides  sodium  chloride  and  sodium  sulphate,  a  fair  pro- 
portion of  sodium  bicarbonate.  Baths  are  provided.  The 
Cheltenham  waters  differ  to  a  considerable  extent  from 
any  other  mineral  waters  found  in  England.  They  are 
fairly  closely  comparable  to  the  waters  of  Marienbad, 
Homburg,  and  Tarasp-Schuls.  The  waters  are  useful  for 
the  same  class  of  cases  as  are  dealt  with  at  Carlsbad, 
Marienbad,  and  Homburg.  Cheltenham  possesses  a  com- 
paratively dry  atmosphere,  and  the  winters  are  mild.  It 
is  especially  suitable  for  those  who  have  lived  long  in 
hot   climates. 

Leamington  (Warwickshire).  The  waters  are  cold. 
Baths  are  provided.  The  waters  are  useful  in  the  treat- 
ment of  torpid  conditions  of  the  liver  and  of  the  gastro- 
intestinal tract  associated  with  gout,  and  also  in  the  treat- 
ment of  gouty  glycosuria. 

4.  Alkaline  muriated  waters. — These  waters  contain 
sodium  bicarbonate  and  sodium  chloride.  They  are  use- 
ful  in   the   treatment   of   gouty   dyspepsia   and   of  gouty 


Chap.  XVI.]  MINERAL    WATERS.  275 

catarrhal  affections  of  the  respiratory  organs.  The  principal 
waters  of  this  class  are  those  of  Ems,  Royat,  Assmanns- 
hausen,  and  La  Bourboule. 

Ems  (Germany).  The  waters  are  hot  (80°  to  120°  F.). 
Altitude  300  feet.  Baths  are  provided.  The  waters  are 
especially  useful  for  patients  suffering  from  gouty  bron- 
chitis and  asthma,  for  the  treatment  of  which  affections 
they  can  be  inhaled  in  a  finely  divided  condition.  They 
may  also  be  employed  in  the  treatment  of  gouty  dyspepsia. 
The  climate  is  a  relaxing  one,  and  is  best  suited  to  elderly 
gouty  patients.  ** 

Royat  (France).  The  waters  are  warm  (68°  to  95° 
F.).  Altitude  1,480  feet.  Baths  are  provided.  The  waters 
are  useful  for  the  same  class  of  cases  as  mentioned  in  con- 
nection with  the  Ems  waters.  The  season  is  from  the 
middle  of  May  to  the  middle  of  September. 

Assmannshausen  (Prussia).  The  water  is  tepid  (82°  F.), 
and  contains  a  small  proportion  of  lithium  bicarbonate. 

La  Bourboule  (France).  The  water  is  hot  (130°  F.). 
Altitude  2,780  feet.  Baths  are  provided.  The  waters 
are  arsenical  as  well  as  alkaline  muriated,  and  may  be 
useful  in  certain  cases  of  chronic  gouty  skin  disorders. 
The  season  is  from  the  beginning  of  June  to  the  end  of 
September. 

5.  Common  salt  or  muriated  waters. — These  waters 
contain  sodium  chloride  as  their  principal  constituent, 
and  some  of  them  also  contain  a  large  amount  of  free 
carbonic  acid  gas. 

Sodium  chloride  has  a  stimulating  effect  upon  the 
mucous  membrane  of  the  gastro-intestinal  tract.  In  the 
stomach  it  dissolves  the  mucus,  increases  the  secretion  of 
gastric  juice,  and  so  helps  to  promote  the  digestion  of 
albuminous  substances.  In  the  intestines  it  stimulates 
the  flow  of  pancreatic  juice  and  bile,  and  owing  to  its 
influence  on  the  process  of  osmosis,  promotes  the  absorp- 
tion of  food.     Intestinal  peristalsis  is  also  increased.     The 


276  GOUT:    TREATMENT.  [partiv. 

waters  are  of  use  in  the  treatment  of  gastro-intestinal  and 
hepatic  gout,  especially  when  accompanied  by  constipation, 
and  in  cases  of  gouty  dyspepsia  associated  with  general 
atony.  They  are  not  indicated  in  cases  of  articular  gout, 
when  the  removal  of  the  uratic  deposits  is  the  main  object 
of  treatment.  The  principal  waters  of  this  class  are  those 
of  Homburg,  Wiesbaden,  Kissingen,  Baden-Baden,  Nau- 
heim,  Llandrindod  Wells,  Woodhall  Spa,  Llangammarch 
Wells,  Oeynhausen. 

Homburg  (Germany).  The  waters  are  cold.  Altitude 
about  600  feet.  Baths,  massage,  and  electrical  treatment 
are  provided.  The  waters  produce  slight  purgation  and 
diuresis,  and  are  useful  for  the  treatment  of  gouty  dyspepsia 
with  a  tendency  to  constipation,  and  of  gouty  gastro- 
intestinal catarrh  and  hepatic  congestion  associated  with 
general  atony. 

Wiesbaden  (Germany).  The  waters  are  hot  (100° 
to  156°  F.).  Altitude  380  feet.  Baths  are  provided. 
The  waters  are  useful  for  the  same  class  of  cases  as  men- 
tioned in  connection  with  the  Homburg  waters,  but  should 
be  avoided  in  cases  of  articular  gout.  Open  throughout  the 
year,  but  in  midsummer  Wiesbaden  is  very  hot. 

Kissingen  (Bavaria).  The  waters  are  cold.  Altitude 
about  600  feet.  Baths  are  provided.  The  waters  are 
useful  for  the  same  class  of  cases  as  mentioned  in  con- 
nection with  the  Homburg  waters.  The  season  is  from 
May  to  the  end  of  September. 

Baden-Baden  (Grand  Duchy  of  Baden).  The  waters 
are  hot  (120°  to  150°  F.).  Altitude  about  650  feet.  Baths, 
douches,  and  electric  baths  are  provided.  The  waters 
are  useful  in  the  treatment  of  gastro-intestinal  catarrh 
and  sluggish  conditions  of  the  liver.  Open  all  the  year, 
but  the  season  is  from  the  beginning  of  May  to  the  end 
of  October.  During  July  and  the  first  half  of  August 
Baden-Baden  is  very  hot. 

Nauheim   (Germany).     The    waters   are  warm  (82°    to 


Chap.  XVI.]  MINERAL   WATERS.  277 

95°  F.).  Altitude  about  400  feet.  This  spa  is  specially 
known  for  its  baths  in  connection  with  the  treatment  of 
various  affections  of  the  heart.  Two  of  the  waters  are 
somewhat  similar  in  composition  to  the  Homburg  water, 
and  may  be  employed  in  the  treatment  of  gouty  dyspepsia. 
The  season  is  from  May  to  the  end  of  September. 

Woodhall  Spa  (Lincolnshire).  This  water,  in  addi- 
tion to  being  a  highly  muriated  water,  contains  bromides 
and  iodides. 

Llangammarch  Wells  (Wales,  Brecknockshire).  Alti- 
tude about  600  feet.  This  water,  in  addition  to  being  a 
muriated  water,  contains  a  small  quantity  of  barium  chloride. 

Brine  baths. — The  brine  baths  of  Droitwich  (England, 
Worcestershire),  Kreuznach  (Germany),  Ischl  (Austria), 
Rheinfelden  (Switzerland),  Aussee  (Styria),  Reichenhall 
(Bavaria),  and  Bourbonne-les-Bains  (France)  are  useful 
in  the  treatment  of  stiffness  and  thickening  of  the  joints 
in  cases  of  chronic  articular  gout,  but  should  be  avoided 
if  gouty  skin  affections  are  present. 

6.  Sulphur  waters. — These  waters  contain  sulphur, 
some  in  the  form  of  sulphuretted  hydrogen  only,  while 
others,  in  addition  to  free  sulphuretted  hydrogen,  contain 
combined  sulphur  in  the  form  ol  the  sulphides  of  calcium, 
magnesium,  and  sodium.  They  are  frequently  very  useful 
in  the  treatment  of  gouty  skin  affections,  especially  eczema 
and  psoriasis.  Sulphur  baths  are  also  of  benefit  for  the 
same  purpose. 

In  my  opinion,  patients  actually  suffering  from  acute 
or  subacute  articular  gout,  or  who  are  apparently  on  the 
verge  of  such  an  attack,  are  better  without  sulphur  waters, 
as  in  such  cases  the  waters  tend  to  accentuate  or  precipitate 
an  attack  in  the  joints.  At  the  present  time,  however, 
it  is  far  commoner  to  meet  with  gout  in  some  of  its  irregular 
forms  than  in  the  articular  form,  and  in  most  of  the  cases- 
of  irregular  gout  the  beneficial  effects  of  sulphur  waters 
are   beyond   question,    and   especially  does   this   apply   to 


278  GOUT:    TREATMENT.  [partiv. 

the  forms  of  gastro-intestinal  catarrh,  hepatic  inadequacy, 
and  eczema  due  to  the  gouty  condition.  The  sulphur 
springs  may  be  classified  into  the  cold  and  hot  springs. 

Cold  sulphur  springs. — The  principal  waters  of  this 
class  are  those  of  Harrogate  (England,  Yorkshire),  Strath- 
peffer  (Scotland),  Llandrindod  Wells  (Wales,  Radnorshire), 
Gurnigel  (Switzerland),  Heustrich  (Switzerland),  Nenndorf 
(Prussia),  and  Weilbach  (Germany). 

Hot  sulphur  springs. — The  principal  waters  of  this 
class  are  those  of  Aix-les-Bains  (France),  Aix-la-Chapelle 
(Germany),  Baden  (Switzerland),  Baden  (near  Vienna), 
Uriage  (France),  Bagneres-de-Luchon  (France),  Allevajd 
(France),  Saint-Honore  (France),  and  Schinznach  (Switzer- 
land). 

Harrogate  (Yorkshire),  The  waters  are  cold.  Alti- 
tude 400  to  600  feet.  The  principal  waters  contain  sul- 
phuretted hydrogen  and  sodium  sulphide.  The  "  Kissingen 
well  "  water  is  a  muriated  chalybeate  water.  Harrogate 
is  well  provided  with  recent  and  elaborate  appliances  for 
baths,  douches,  etc.  The  waters  are  especially  useful 
in  the  treatment  of  the  various  forms  of  gastro-intestinal 
catarrh,  hepatic  inadequacy,  and  eczema  due  to  the  gouty 
condition.  The  various  baths  are  extremely  beneficial 
in  the  removal  of  the  stiffness  and  swelling  of  the  joints 
left  after  an  attack  of  gout.  The  spa  is  open  all  the  year, 
but  the  season  lasts  from  May  to  September. 

Llandrindod  Wells  (Wales).  The  waters  are  cold. 
Altitude  700  feet.  The  waters  are  somewhat  similar  to 
those  of  Harrogate,  and  are  used  for  the  same  class  of 
cases.     The  season  is  from  May  to  October. 

Strathpe-ffer  (Scotland).  The  waters  are  cold.  Alti- 
tude 200  feet.  The  principal  waters  contain  sulphuretted 
hydrogen  and  sodium  sulphide,  and  are  used  for  the  same 
class  of  cases  as  the  Harrogate  waters.  Various  kinds  of 
baths,  including  peat  baths,  are  provided.  The  spa  is 
open  all  the  year,  but  the  season  lasts  from  May  to  October. 


Chap.  XVI.] 


MINERAL  WATERS. 


279 


Aix-les-Bains  (France).  The  waters  are  hot  (112''  F.). 
Altitude  870  feet.  The  waters  contain  free  sulphuretted 
hydrogen.  This  spa  is  especially  known  for  its  baths, 
douches,  and  douche-massage,  all  of  which  methods  of 
treatment  are  most  beneficial  in  the  removal  of  the  stiff- 
ness and  swelling  of  the  joints  left  after  an  attack  of  gout. 
The  waters  are  also  employed  in  the  treatment  of  cutaneous 
affections  connected  with  gout.  The  spa  is  open  all  the 
year,  but  the  season  lasts  from  April  to  November. 

Hot  and  cold  mineral  waters. — The  following  table 
shows  a  classification  of  the  various  mineral  waters  used 
in  the  treatment  of  gout  into  hot  and  cold  waters  :— 


.     TABLE    LXI. 

Classification   of  the   various   mineral  waters    used    in    the    treatment 
of  gout  into  hot  and  cold  waters. 


Hot. 

Cold. 

Aix-les-Bains 

Cheltenham 

Aix-la-Chapelle 

Contrexeville 

Baden 

Harrogate 

Baden-Baden 

Homburg 

Bath 

Kissingen 

Brides-les-Bains 

Leamington 

Buxton 

Llandrindod  Wells 

Carlsbad 

Marienbad 

Ems 

Salzbrunn 

Gastein 

Strathpeffer 

La  Bourboule 

Tarasp-Schuls 

Nauheim 

Vals 

ITeuenahr 

Vichy  (some  springs) 

Ragatz-Pfaefers 

Vittel 

Royat 

Teplitz 

Vichy  (some  springs) 

. 

Wiesbaden 

Wildbad 

Choice  of  a  spa. — In  the  selection  of  a  spa,  so  many 
factors  have  to  be  considered  that  it  is  impossible,  in  a 
work  of  this  nature,  to  deal  fully  with  the  subject.     I  wish, 


28o 


GOUT:    TREATMENT. 


Part  IV. 


however,  to  state  clearly  that  the  high  state  of  efficiency 
to  which  our  home  spas  have  been  raised  renders  it  no 
longer  essential  to  banish  our  patients  to  foreign  health 
resorts,  and  that,  unless  a  complete  change  of  environ- 
ment is  desired  by  the  patient  or  is  essential  to  recovery, 
treatment  can,  in  the  great  majority  of  cases,  be  carried 
out  as  effectually  in  our  own  country. 

The  following  table  may  be  of  some  value  as  an  attempt 
to  classify  the  therapeutic  indications  of  mineral  waters  in 
the  treatment  of  gouty  conditions. 

TABLE  LXII. 

Classification     of    the     various    mineral   waters   according    to    their 
therapeutic  value  in  the  treatment  of  the  variotis  forms  of  gout. 


Object  of  taking  the 
waters. 


Absorption  of  gouty 
deposits  from  the  joints 
and  tissues. 


The  waters  best  suited  to  the  purpose. 


Bath,  Buxton,  Contrexeville,  Gas- 
tein,  Harrogate,  Pfaefers,  Strathpeffer, 
Teplitz,  Vittel,  Wildbad,  Aix-les-Bains 
(for  baths). 


Treatment      of      gouty 
dyspepsia. 


Brides-les-Bains,  Carlsbad,  Ems, 
Harrogate,  Homburg,  Kissingen, 
Neuenahr,  Royat,  Vals,  Vichy,  Wies- 
baden. 


Treatment  of  gouty 
congestion  and  torpor  of 
the  liver,  and  of  gastro- 
intestinal catarrh  and  tor- 
por. 


Baden-Baden,  Bourbonne,  Carlsbad, 
Cheltenham,  Contrexeville,  Harrogate, 
Homburg,  Kissingen,  Leamington, 
Llandrindod  Wells,  Marienbad,  Neuen- 
ahr, Tarasp-Schuls,  Vals,  Vichy,  Vittel, 
Wiesbaden. 


Treatment  of  gouty 
affections  of  the  respira- 
tory organs. 


Ems,   Royat. 


Treatment  of  gouty  gly- 
cosuria and  diabetes. 


Carlsbad,  Contrexeville,  Harrogate, 
Kissingen,  Leamington,  Llandrindod 
Wells,  Marienbad,  Neuenahr,  Strath- 
peffer,  Vals,  Vichy,  Vittel. 


Treatment  of  gouty  skin 
affections. 


Aix-les-Bains,  Baden,  Bagneres-de- 
Luchon,  Harrogate,  Llandrindod 
Wells,  Schinznach,  Strathpeffer. 


Chap.  XVI.]  BALNEOLOGY.  281 

Balneolog'y. — Useful  as  may  be  the  drinking  of  a 
water  at  a  spa,  yet  equally,  and  even  in  some  cases  more, 
useful  is  the  encouragement  for  therapeutic  purposes  of 
the  functions  of  the  skin  by  balneological  methods.  The 
skin  is  the  largest  organ  of  the  body,  and,  as  would  be 
expected  of  such  an  organ,  it  possesses  various  and  com- 
plex functions.  Amongst  its  functions  are  (i)  the  ex- 
cretion of  toxic  bodies,  the  retention  of  which  proves 
harmful  and  ultimately  fatal  to  the  organism  ;  (2)  the 
power  that  it  possesses  through  its  nerve-endings  of  stimu- 
lating distant  organs  and  tissues  ;  and  (3)  its  heat-regu- 
lating power.  The  success  of  balneology,  whether  in  the 
treatment  of  chronic  joint  conditions,  of  affections  of 
the  fibrous  tissues,  of  certain  heart  and  kidney  affections, 
or  of  certain  skin  diseases,  depends  upon  the  recognition 
of  the  powerful  aid  which  can  be  given  by  the  skin  in 
restoring  the  normal  balance. 

Heat,  whether  applied  in  the  form  of  water  baths  or 
in  that  of  air  baths,  lowers  the  arterial  pressure  and  raises 
the  venous  pressure,  as  a  consequence  of  the  relaxation 
of  the  muscular  coats  of  the  arteries  and  of  the  arterioles 
that  is  induced. 

The  flushing  effect  of  a  course  of  warm  baths  on 
the  clogged  periphery  of  the  circulation  is  useful  in 
chronic  gout  and  in  chronic  renal  disease,  and  this  bene- 
ficial influence  extends  to  the  heart,  since  the  opening 
up  of  the  peripheral  circulation  eases  the  work  of 
the  left  ventricle,  which  consequently  is  able  to  deliver 
its  load  more  and  more  completely,  and  retain  less 
and  less  residual  blood  as  the  peripheral  resistance 
diminishes. 

The  cabinet  electric  light  bath  in  which  the  whole 
body  is  enclosed  up  to  the  neck  is  a  powerful  means  for 
the  reduction  of  the  arterial  blood  pressure,  and  is  service- 
able in  the  treatment  of  high  arterial  pressure,  such  as 
that   observed  in  granular  kidney.       In    addition    to    its 


282  GOUT:    TREATMENT.  [Partiv. 

pronounced  action  on  the  circulation,  it  is  a  powerful 
stimulant  of  the  cutaneous  excretion  of  waste  products. 

Warm  baths  are  of  great  therapeutic  value  as  vaso- 
motor relaxants,  but  there  is  another  group  of  baths  possess- 
ing quite  different  properties — namely,  those  of  cardiac 
and  vaso-motor  stimulation.  These  are  percussive  baths, 
massage  baths,  and  baths  of  alternating  temperature. 

Percussive  baths  are  represented  by  the  various  forms 
of  douche  and  needle  baths.  The  general  effect  on  the 
blood  pressure  is  to  raise  the  arterial  and  to  lower  the 
venous  pressure.  George  Oliver  states  that  the  needle 
bath,  doubly  alternating  in  temperature  {i.e.  falling  from 
warm  to  cool,  then  rising  to  warm,  and  again  falling  to 
cool),  with  a  hot  descending  spinal  douche,  has  the  most 
powerful  effect  in  raising  the  arterial  pressure.  There  is 
no  doubt  that  the  effect  of  the  percussion  of  water  on 
the  peripheral  vessels  is  greatly  intensified  -  by  varying  the 
temperature,  and  especially  by  allowing  it  to  dip  to  the 
lowest  ranges.  Apart  from  percussion,  the  mere  alteration 
of  temperature,  when  considerable,  has  a  remarkable  effect 
on  the  blood  pressure,  and  especially  is  this  the  case  when 
the  cold  plunge  is  taken  either  after  a  very  hot  water  bath, 
or  after  a  hot-air  or  Turkish  bath.  It  is  on  this  account 
that  the  subjects  of  advanced  chronic  gout,  associated 
with  high  arterial  tension,  should  avoid  the  cold  plunge, 
and  the  cold  needle  bath  or  douche  after  a  hot  bath. 

Climatic  treatment. — A  fairly  bracing  air  with  a  low 
relative  humidity  is,  in  my  experience,  the  most  suitable 
for  the  gouty.  High  mountain  situations,  and  valleys 
where  there  is  an  excessive  relative  humidity  of  the  air, 
are  alike  unsuited  to  the  gouty.  Especially  is  it  desirable 
to  avoid  exposure  to  the  cold  east  and  north-east  winds 
which  prevail  in  this  country  in  the  early  months  of  spring, 
and  which  are  so  apt  to  be  provocative  of  what  has  been 
called  a  "  chill  on  the  liver,"  a  condition  which  no  doubt 
is   brought   about  by  the   chilling  effects  of  these  winds 


Chap.  XVI.]  CLIMATIC    TREATMENT.  283 

on  the  skin,  and  a  consequent  reflex  affection  of  the  meta- 
boHsm  of  the  liver  cells. 

A  typically  bracing  climate  is  provided  by  a  place 
which  is  exposed  and  elevated,  which  has  a  low  relative 
humidity,  and  is  therefore  liable  to  rapid  variations  of 
temperature.  A  typically  relaxing  or  sedative  climate  is 
one  in  which  the  opposite  conditions  prevail.  It  is  shel- 
tered and  low-lying,  with  a  high  degree  of  relative  humidity, 
and  is  therefore  remarkably  equable,  both  seasonally  and 
diurnally.  The  physiological  effect  of  a  bracing  climate 
is  to  increase  metabolism,  of  a  relaxing  climate  to  diminish 
metabolism. 

There  are  some  types  of  gout  which  benefit  conspicu- 
ously from  bracing  climates,  but  these  are  the  less  pro- 
nounced types,  in  which  stimulating  conditions  may  be 
tried  without  danger.  On  the  other  hand,  those  types  of 
gout  which  are  associated  with  chronic  renal  disease,  and 
older  patients  suffering  from  arterio-sclerosis  and  high 
arterial  tension,  are  best  treated  by  sedative  climates.  In 
cases  of  chronic  renal  disease,  care  must  be  taken  to  avoid 
any  sudden  or  extreme  change  of  temperature,  which  would 
impose  an  undue  strain  on  the  damaged  kidneys.  It  is 
in  such  cases  that  relaxing  climates  are  frequently  of 
immense  benefit.  In  cases  of  gout  associated  with  fatty 
degeneration  of  the  heart  or  with  valvular  disease,  a  seda- 
tive climate  is  most  desirable. 

All  gouty  individuals  should  avoid  localities  in  which 
there  are  hard  chalky  waters,  or,  if  they  have  to  reside 
in  such  localities,  should  avoid  drinking  the  water  of  the 
district.  In  such  cases  they  should  drink  distilled  water, 
plain  or  aerated,  or  some  of  the  simple  natural  mineral 
waters.  As  a  winter  resort  for  the  gouty  I  know  of  no 
better  climate  than  that  of  Egypt,  where,  at  Helwan 
(Helouan),  thermal,  sulphurous,  and  saline  waters  exist, 
and  excellent  baths  are  obtainable.  The  air  of  Helwan 
is  that  of  the  desert,  and  almost  germ  free.     The  winter 


284  GOUT:    TREATMENT.  [partiv. 

sunshine  averages  eight  hours  a  day  ;  the  average  winter 
temperature  is  60°  F.  at  9  a.m.  and  9  p.m.,  70°  F.  at  3  p.m., 
and  50°  F.  at  the  coldest  time  of  the  night,  and  the  relative 
humidity  from  November  to  April  only  30  to  60  per  cent. 
There  is  not  much  wind,  and  the  amount  of  dust  is  less 
than  in  most  parts  of  Egypt,  while  the  average  rainfall 
for  four  consecutive  winters  was  only  three-quarters  of 
an  inch.  For  the  spring,  summer,  and  autumn  months 
we  fortunately  have  for  our  selection  a  large  number  of 
health  resorts  in  this  country  and  on  the  Continent,  the 
climates  of  which  are  well  suited  to  the  gouty.  My  ex- 
perience is  that  residence  by  the  sea  is  not  suited  to  most 
cases  of  gout,  and  this  especially  applies  to  cases  of  gouty 
eczema. 


INDEX. 


Abarticular  gout,  130-146 

Acidity  and  gout,  208-211 

,  Treatment  of  gouty,  232 

Acute     gout.    Clinical     features    of, 
106-108 

Diet  in,  220,  221 
Treatment  of,  217-221 

Adenin,  10 

/Etiology  of  gout,   101-106 

Age  and  gout,  loi 

Aix-les-Bains  waters,  279 

Albuminuria  and  gout,  108-111 

Alcohol,  260-263 

Alkaline  muriated  waters,  274,  275 

sulphated  waters,  273,  274 

waters,  Simple,  272,  273 

Alkalinity  of  the  blood,  70,   71 
AUantoin,   16 

Allevard  waters,  278 
AUoxur  bases  and  gout,  47,  48 
Amorphous  urate  deposit,    117-119 
Angina  pectoris  and  gout,   137 

,  Treatment  of  gouty,  234 

Animal  diet  and  uric  acid,   38-40 

food,  247-249 

Arthritic   disease,    Classification    of, 
147.  148 

diseases.  Differential  diagnosis 

of,  147-170 

Arthritis,  Gonorrhoeal,   161,   162 

,  Malarial,    163 

,  Pneumococcic,    163 

,   Rheumatoid,    149-155 

,  Scarlatinal,    163 

Arthropathies,   Infective,  162,  163 
- — — ,   Senile,    160,    161 
Assmannshausen  waters,  275 
Asthma,  Gouty,  134 


B 


Bacillus  coli  communis  and  gout,  61, 

63 
Bacterial  origin  of  gout,  59-64 
Baden-Baden  waters,  276 


Baden  waters,  278 
Bagneres-de-Luchon  waters,  278 
Balneology,  281,  282 
Bath,   Electric  light,   228-230 

,   Superheated-air,  228-230 

Bath  waters,   271 
Baths,  281,  282 

,  Percussive,  282 

Beverages,  252,  253 

Biurates,  2,  3 

Bladder,  Gouty  irritability  of,  141 

Blood,  Detection  of  uric  acid  in,  67 

diseases  and  uric  acid,  69,  70 

,  Uric  acid  a  normal  constituent 

of,  66-70 
Brachial  neuritis.  Gouty,    139,    140 
Brides-les-Bains  waters,   274 
Brine  baths,  277 
Bronchitis,   Gouty,    134 
Buxton  waters,  271 


Caffein,  10 

Calculi,  Uric  acid,   141 
Carbohydrate  foods,  249-251 
Cardiac  gout,   135-137 
Carlsbad  waters,  273 
Cartilage,  Seat  of  deposit  in,  98,  99 
Cataphoresis,  230 
Cheltenham  waters,  274 
Chittenden's  views,  245,   246 
Choice  of  a  spa,  279,  280 
Chronic    gout.    Clinical    features   of, 
108-111 

,  Treatment  of,  221-231 

Cider,  263 

Climatic  treatment,  282-284 
Colchicum,  Action  of,  219,  220 

in  gout,  219,  220 

Common  salt  waters,  275-277 
Conjunctivitis,  Gouty,  144 
Contrexeville  waters,  271 


D 


Diabetes,  Gouty,  144 

,  Treatment  of  gouty,   238,  239 


285 


286 


INDEX. 


Diagnosis  of  gout  from  rheumatoid 

arthritis,   157-159 
Diet,  Animal,  247-249 

for  the  gouty,  256-258 

in  acute  gout,  220,  221 

in  gout,  241-258 

Dieting,   General  principles  of,   241- 

244 
Digestibility  of  food,  242-244 
Dimmock-Branson's  method,  121-125 
Douche,  Scotch,  227 
Droitwich  brine  baths,  277 
Dupuytren's  contraction,   170 
Dyspepsia,  Gouty,   132 
,  Treatment  of  gouty,  232 


E 


Ear  and  gouty  deposits,  91 

diseases  and  gout,  144 

Ebstein-'s  views  and  experiments,  48- 

,  Criticism  of,  50-53 

Eczema,  Gouty,  142 

,  ,  Treatment  of,  236-238 

Egypt,  283 

Electric  light  bath,  228-230 
Electrolysis,  231 
Ems  waters,  275 
Endogenous  purins,   12,   13 
Epididymitis,   Gouty,    141,   142 
Epilepsy  and  gout,  140 
Estimation  of  uric  acid,   1 19-125 
Exogenous  purins,   13-17 
Eye  affections  and  gout,  144 


Fibrositis,  Distinction  of  gout  from, 
165-170 

,  Forms  of,  165-170 

Food,  Animal,  247-249 

,   Digestibility  of,  242-244 

— ,   Saccharine,  251 

-,   Starchy,   249-251 

,  Vegetable,  249 

Fruits,   251,  252 


Galvanism  of  gouty  joints,  227 
Gastein  waters,  271 
Gastralgia,    Gouty,    132 
Gastric   gout,   134 
Gastro-intestinal  gout,  133,  134 


Garrod's  thread  test,  67 
Geographical    distribution    of    gout, 

lOI 

Glycocine  and  uric    acid   formation, 

27 
Glycosuria,  Gouty,  144 

,   Treatment  of  gouty,   238,   239 

Gonorrhoeal  arthritis,  161,    162 
Gout,  Abarticular,   130-146 

,  Acute,   106-108 

,  Etiology  of,   101-106 

,  Alkalinity  of  blood  in,   70,  71 

and  habits  of  life,   104,  105 

lead,   125-129 

— ■ — ■   plumbism,    125-129 

rheumatism.    Distinction 

of,    165-170 

rheumatoid         arthritis, 

Differential  diagnosis  of,  157-159 

Bacterial  origin  of,    59-64 

Causation  of,  4-64 

Chronic,   108-111 

,  deforming,   109 

Definition  of,   i 

Development  of,    i,  2 

Diet  in  acute,  220,  221 

Exciting  cause  of,  106 

Gastric,   134 

Gastro-intestinal,   133,   134 

Irregular,  130-146 

Metastatic,  145,  146 

Preventive  treatment  of,  225, 
226 

Primary  causation  of,  41-65 

Principles  of  treatment  of,  215 
216 

Prognosis  in,    171 

Retrocedent,    145,    146 

Tophaceous,   109 

Treatment  of  acute,  217-221 

chronic,   221-231 

subacute,  221-231 

Urine  in,    109-119 

Gouty  angina.  Treatment  of,  234 
asthma,   134 

attack,  Duration  of,   107,   108 
bronchitis,    134 
deposit,  Formation  of,  85-91 
deposits.    Seats  of,   91,    92 
diabetes,   144 
dyspepsia,   132 
eczema,   142 

Treatment  of,   236-238 
epididymitis,    141,    142 
gastralgia,   132 
glycosuria^  144 
heart,    135-137 

,  Treatment  of,  233,  234 

herpes,  143 
hyperchlorhydria,  132,  133 


INDEX. 


287 


Gouty  joints,  Treatment  of,   226-231 

kidney,  140,  141 

laryngitis,    134 

neuralgia,  139 

neuritis,   139,   140 

,   Treatment  of,    235 

■    orchitis,  141,  142 

parotitis,   132 

paroxysms.  Treatment  of,  217- 

219 

pharyngitis,    131,    132 

phlebitis,    138,    139 

,  Treatment  of,  235 

pruritus,    143 

sciatica,  139 

,  Treatment  of,  235 

tonsillitis,    131 

tracheitis,    134 

Govvland-Hopkins  method,    120,   121 
Gravel,  Uric  acid,  141 
Guaiacum  resin  and  gout,  221 
Guanin,  10 

Gurnigel  waters,  278 


H 


Harrogate  waters,  27S 
Hay-fever  and  gout,  145 
Heart,    Gouty,   135-137 

,  Treatment  of  gouty,  233,  234 

Heberden's  nodes,  151,  152 

Helwan  waters,  283 

Hepatic  congestion  and  gout,  145 

torpor,  Treatment  of,   233 

Hereditary  predisposition,  102-104 
Herpes,  Gouty,  143 
Heustrich  waters,  278 
Homburg  waters,  276 
Hyperchlorhydria,  Gouty,   132,  133 

,  Treatment  of,  232 

Hyperpyraemia,  57-59 
Hypoxanthin,  6 


I 


Imperial  drink,  253 

Inflammatory  changes  and  gout,  53- 

55 
Insomnia  and  gout,    140 

,  Treatment  of,  236 

Intestinal  bacteria  and  gout,  61-64 
Ionic  theory,  266,  267 
Iritis,   Gouty,   144 
Irregular  gout,    130-146 

,   Forms  of,    130-146 

Irritable  temper  in  gout,  Treatment 

of,  236 


J 


Joint  diseases  and  gout,  147-170 

,  Classification  of,  147,  148 

— ■ — •   ,   Differential  diagnosis  of, 

147-170 
Joints,   Treatment  of  gouty,   226-231 


K 


Kidney  affections  and  gout,   29-35 

disease  and  uratic  deposits,  30- 

33 

,  Gouty,  140,  141 

Ividneys    and    uric    acid    formation, 

24-34 

in   chronic   gout,    109-111 

Kissingen  waters,  276 


La  Bourboule  waters,  275 
Laryngitis,  Gouty,  134 
Lead  and  gout,  125-129 

poisoning  and  gout,  34,  35 

Leamington  waters,  274 
Leucocytosis  and  uric  acid,  7-9 
Leukaemia  and  uric  acid,  69,  70 
Lithium    salts    and    gout,    207,    208, 

222 
Liver  and  destruction  of  toxins,  64, 

65 

and  uric  acid  formation,  35-37 

,   Congestion  of,    145 

diseases   and   uric   acid   forma- 
tion,  28 

Llandrindod  Wells  waters,  278 
Llangammarch  Wells  waters,  277 
Lumoago,    169,   170 
Lymph  circulation,  92-97 
Lysidine  and  sodium  biurate,  206 


M 


Malarial  arthritis,   163 
Marienbad  waters,  273 
Massage  of  gouty  joints,  226-228 
Meals,  Simplicity  of,   253-255 
Meat  diet,  247-249 

,  Mineral  constituents  of,   173 

Mental  depression  and  gout,   140 
Metastatic  gout,   145,    146 

— — ■,   Treatment  of,  239,  240 

Migraine  and  gout,  139 


288 


INDEX. 


Mineral  waters,    268-280 

■ — —   -' ,  Classification  of,  269,  270 

,  Cold,  279 

Hot,  279 
Radio-activity     of,     267, 

Simple,    270-272 

■   — — •,  Therapeutic  uses  of,  280 

Murexide  test,  4 
Muriiited  waters,  275-277 

,  Alkaline,  274,  275 


N 


Nauheim  waters,  276 

Necrotic  changes  and  gout,  48-53 

Nenndorf  waters,  278 

Nervous  disturbance  and  gout,  55-57 

Neuenahr  waters,  272 

Neuralgia,  Gouty,    139 

Neuritis,  Gouty,    139,   140 

,  ,  Treatment  of,  235 

Neuro-humoral  view  of  gout,  55-57 

Nucleic  acid,  9 

Nuclein  formation  of  uric  acid,  5-10 


O 


Orchitis,  Gouty,  141,   142 
Osteo-arthropathy,  Pulmonary,   165 
Otto  Folin  method,  121 


Parotitis,  Gouty,  132 
Percussive  baths,  282 
Perry,  264 
Pfaefers  waters,  271 
Pharyngitis,  Gouty,  131,  132 
Phlebitis,  Gouty,   138,  139 

,  ,  Treatment  of,   235 

Piperazine  and  sodium  biurate,   205 
Plumbism  and  gout,   125-129 
Pneumococcic  arthritis,  163 
Potassium  salts  and  gout,  221,  222 
Potato,  250 
Preventive   treatment  of   gout,    221;, 

226 
Prognosis  in  gout,   171 
Prophylactic  treatment  of  gout,   225, 

226 
Pruritus,  Gouty,  143 


Psoriasis  and  gout,  143 
Pulmonary  osteo-arthropathy,  165 
Purin  bodies,   10-23 

and  absorption,   18,   19 

■  — ■ — '  blood    pressure,    17, 

18 

• food,   14-16 

uric  acid,    19 

,  Origin  of,   n 

Purin-free  diet,   14,   15,  248,  249 
Purins,    Endogenous,    12,    13 

,   Estimation  of,   22,   23 

,   Exogenous,    13-17 


Q 


Quadriurates,  2-4 


R 


Radio-activity  of  mineral  waters,  267, 

268 
Raynaud's  disease,  165 
Renal  calculi,  Treatment  of,  236 
Renal  disease  and  gout,  29-35 

uratic  deposits,  30-33 

Retrocedent  gout,    145,    146 

,  Treatment  of,   239,    240 

Rheumatic  diseases  of  joints,  155-157 
Rheumatism,   155-157 

,  Chronic,    165-170 

,  Distinction  of  gout  from,  165- 

170 
— ■ — -,  Muscular,  169 
Rheumatoid  arthritis,    149-155 
and     gout.     Differential 

diagnosis  of,    157-159 
Royat  waters..  275 


Saccharine  food,  251 
Saint  Honore  waters,   278 
Salicylates  and  gout,  21 1-2 14 
Salisbury  diet,  255,   256 
Salt  pack,  227,  228 
Salzbrunn  waters,  272 
Saturnine  gout,  125-129 
Scarlatinal  arthritis,   163 
Schinznach  waters,  278 
Sciatica,  Gouty,  139 

,  Treatment  of  gouty,  235 

Scotch  douche,  227 


INDEX. 


289 


Sex  and  gout,    loi 
Simplicity  of  meals,   253-255 
Simple  alkaline  waters,   272,   273 

mineral  waters,  270-272 

Skin  eruptions  and  gout,   142-144 
Sodium  biurate  and  alkalies,  201-204 
alkalinity     of     the 

blood,  71-84 

as  an  irritant,  41-45 

,   Deposition  of,  87-91 

quadriurate,   86 

and  alkalies,  199,  200 

Solvents  of  uric  acid,  224 

Spa,  Choice  of,  279,  280 

treatment,   265-269 

Spirits,  259,  260 

Spleen   and   uric   acid    formation,    36 

Starchy  food,  249-251 

Still's  disease  of  the  joints,   159,   160 

Strathpeffer  waters,  270,  278 

Streptococci  and  gout,  63 

Subacute   gout.    Treatment  of,    221- 

231 
Sugar  as  food,   251 
Sulphated  waters.  Alkaline,  273,  274 
Sulphur  springs,  Cold,  278 
,   Hot,  278 

waters,  277-279 

Superheated-air  bath,   228-230 
Syphilitic  joint  disease,   164,   165 


Tarasp-Schuls  waters,   274 

Teplitz  waters,   270 

Theobromin,   10 

Thymic  acid,  9 

Toe  and  gouty  deposits,  91 

Tonsillitis,   Gouty,    131 

Tophaceous  gout,    109 

Tophi,   98,   109 

Toxicity  of  uric  acid,  45-47 

Tracheitis,  Gouty,   134 

Treatment  at  spa,  265-269 

by  mineral  waters,  268-280 

,   Climatic,  282-284 

of  acute  gout,  217-221 

chronic  gout,  221-231 

gout,   Principles  of,  215, 

216 

gouty  angina,    234 

diabetes,  238,  239 

dyspepsia,   232 
eczema,  236-238 
glycosuria,  238,  239 
heart,  233,   234 
joints,   226-231 
neuritis,    235 


Treatment  of  gouty  phlebitis,  235 

sciatica,  235 

hepatic  torpor,   233 
hyperchlorhydria,  232 
insomnia,   236 
metastatic  gout,  239,  240 
retrocedent     gout,     239, 
240 

subacute  gout,  221-231 

Tuberculous  joint  disease,  164 

Turkish  bath,   230 


U 
Urates,    2,   3 

Uratic  deposits,   Seats  of,   91 
Uriage  waters,   278 
Uric  acid  and  animal  diet,  38-40 

blood  diseases,   69, 


70 


blood,  5 


its  compounds,  2-4 

nuclein,   5-10 

purins,   19 

calculi,    141 

Cause  of  presence  of,  in 


67 


112-117 


34 


Destruction  of,   13 
Detection    of,    in    blood. 

Estimation  of,  119-125 
Excretion    of,    in    gout, 

gravel,    141 

in  blood,  66-70 

not  toxic,   45-47 

Renal  formation  of,   24- 


Solvents  of,  224 
Urinary  purins.  Estimation  of,  22,  23 
Urine,  Amorphous  urate  deposit  of, 

117-119 

,   Estimation  of,  119-125 

,   Estimation  of  purins  in,  22,  23 

',   Estima'tion    of    uric    acid    in, 

119-125 
,   Examination  of,   216,  217 

in  gout,  109-119 

of  chronic  gout,   109-111 

Urticaria,  Gouty,   143 


Vals   water,  272 

Vegetable  ashes,  Alkalinity  of,   182 

food,  249 

Vegetables   and    gout,    172-197 
,   CalciMm   salts  in,    187 


290 


INDEX. 


Vegetables,  Chlorides  in,  190 

for  the  gouty,  197 

,  Mineral  constituents  of,   175 

,  Phosphates  in,  188 

,  Potassium  salts  in,    184,    185 

,   Sodium    salts  in,    185,    186 

,  Sulphates  in,   189 

Vertigo  and  gout,   140 
Vichy  waters,  272 
Vittel  waters,  272 


W 

VVeilbach  waters,   278 
Wiesbaden  waters,  276 
Wildbad  waters,  271 
Wines,  260-263 
Woodhall  Spa  waters,  277 


X 


Xanthin,  6 


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